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Antidiabetic effect of Achillea millefollium through multitarget interactions: α-glucosidases inhibition, insulin sensitization and insulin secretagogue activities
Abstract
Ethnopharmacological importance:
Achillea millefolium L. (Asteraceae) is a perennial herb used in Mexican folk medicine for treatment of several pathologies, including inflammatory and spasmodic gastrointestinal disorders, hepatobiliary complaints, overactive cardiovascular, respiratory ailments and diabetes.
Aim of the study:
To evaluate the potential antidiabetic effect in vivo and to establish the potential mode of action through in vitro approaches of Achillea millefolium.
Materials and methods:
The antidiabetic effect of hydroalcoholic extract of Achillea millefolium (HAEAm) was evaluated on the oral glucose tolerance tests, in normoglycemic and experimental Type 2 diabetic mice models. In addition, we evaluated the possible mode of action in in vitro assays to determine α-glucosidases inhibition, the insulin secretion and calcium mobilization in RINm5F cells and PPARγ and GLUT4 expression in 3T3-L1 cells.
Results:
HAEAm showed significant glucose diminution on oral glucose tolerance test and in acute experimental Type 2 diabetic assay with respect to the control (p<0.05). In addition, HAEAm promoted the α-glucosidases inhibition by 55% at 1mg/ml respect to control. On the other hand, HAEAm increased the PPARγ (five-times) and GLUT4 (two-fold) relative expression than control (p<0.05). Finally, HAEAm significantly increased the insulin secretion and [Ca(2+)]i compared with control.
Conclusion:
The HAEAm possesses in vivo antidiabetic effect, having such effect through multitarget modes of action that involve antihyperglycemic (α-glucosidases inhibition), hypoglycemic (insulin secretion) and potential insulin sensitizer (PPARγ/GLUT4 overexpression) actions.
... Another study by Chávez- suggests that the hydroethanolic extract of A. millefolium probably induces its antidiabetic function via the PPARγ (activating peroxisome proliferator-activated receptors)/GLUT4 pathway, improving sensitivity to insulin and promoting the expression of glucose metabolism genes, such as GLUT4, which allow glucose to be transported into the cell, resulting in its reduction in the blood [407]. On the other hand, Zolghadri et al. (2014) reported that the ethanolic extract of A. millefolium significantly decreased the expression of IL-1β and iNOS (inducible Nitric Oxyde Synthase) genes against the cytotoxic effect induced by STZ on pancreatic β cells, and those increasing insulinemia [408]. ...
... On the other hand, Zolghadri et al. (2014) reported that the ethanolic extract of A. millefolium significantly decreased the expression of IL-1β and iNOS (inducible Nitric Oxyde Synthase) genes against the cytotoxic effect induced by STZ on pancreatic β cells, and those increasing insulinemia [408]. Furthermore, as a result, it was persistent throughout the experiments in the oral glucose tolerance test and the STZ diabetic model; this suggests another mode of function that participates as an extrapancreatic contribution, which could induce insulin sensitisation [407]. According to Chávez-Silva et al. (2018), these results could be related to PPARγ activation, as there is evidence that this decreases inflammatory cytokines [IL-6, TNF-α (Tumour Necrosis Factor), IL-1β, IL-10, IL-12, and gelatinase B]. ...
... According to Chávez-Silva et al. (2018), these results could be related to PPARγ activation, as there is evidence that this decreases inflammatory cytokines [IL-6, TNF-α (Tumour Necrosis Factor), IL-1β, IL-10, IL-12, and gelatinase B]. It decreases iNOs and scavenger receptor A gene expression [407]. [173] ...
The Serra da Estrela Natural Park (NPSE) in Portugal stands out as a well-preserved region abundant in medicinal plants, particularly known for their pharmaceutical applications in diabetes prevention and treatment. This comprehensive review explores these plants' botanical diversity, traditional uses, pharmacological applications, and chemical composition. The NPSE boast a rich diversity with 138 medicinal plants across 55 families identified as traditionally and pharmacologically used against diabetes globally. Notably, the Asteraceae and Lamiaceae families are prevalent in antidiabetic applications. In vitro studies have revealed their significant inhibition of carbohydrate-metabolizing enzymes, and certain plant co-products regulate genes involved in carbohydrate metabolism and insulin secretion. In vivo trials have demonstrated antidiabetic effects, including glycaemia regulation, insulin secretion, antioxidant activity, and lipid profile modulation. Medicinal plants in NPSE exhibit various activities beyond antidiabetic, such as antioxidant, anti-inflammatory, antibacterial, anti-cancer, and more. Chemical analyses have identified over fifty compounds like phenolic acids, flavonoids, terpenoids, and polysaccharides responsible for their efficacy against diabetes. These findings underscore the potential of NPSE medicinal plants as antidiabetic candidates, urging further research to develop effective plant-based antidiabetic drugs, beverages, and supplements.
... Another study by Chávez- suggests that the hydroethanolic extract of A. millefolium probably induces its antidiabetic function via the PPARγ (activating peroxisome proliferator-activated receptors) / GLUT4 pathway, improving sensitivity to insulin and promoting the expression of glucose metabolism genes, such as GLUT4, which allow glucose to be transported into the cell, resulting in its reduction in the blood [415]. On the other hand, Zolghadri et al. (2014) reported that ethanolic extract of A. millefolium significantly decreased the expression of IL-1β and iNOS (inducible Nitric Oxyde Synthase) genes against the cytotoxic effect induced by STZ on pancreatic β cells, and those increasing insulinemia [416]. ...
... On the other hand, Zolghadri et al. (2014) reported that ethanolic extract of A. millefolium significantly decreased the expression of IL-1β and iNOS (inducible Nitric Oxyde Synthase) genes against the cytotoxic effect induced by STZ on pancreatic β cells, and those increasing insulinemia [416]. Furthermore, as a result, it was persistent throughout the experiments in the oral glucose tolerance test and the STZ diabetic model; this suggests another mode of function that participates as an extrapancreatic contribution, which could induce insulin sensitisation [415]. According to Chávez-Silva et al. (2018), these results could be related to PPARγ activation, which there is evidence decreases inflammatory cytokines [IL-6, TNF-α (Tumour Necrosis Factor), IL-1β, IL-10, IL-12 and gelatinase B]. ...
... According to Chávez-Silva et al. (2018), these results could be related to PPARγ activation, which there is evidence decreases inflammatory cytokines [IL-6, TNF-α (Tumour Necrosis Factor), IL-1β, IL-10, IL-12 and gelatinase B]. It decreases iNOs and scavenger receptor A gene expression [415]. ...
The Serra da Estrela Natural Park (NPSEs) in Portugal stands out as a well-preserved region abundant in medicinal plants, particularly known for their pharmaceutical applications in diabetes prevention and treatment. This comprehensive review explores these plants' botanical diversity, traditional uses, pharmacological applications, and chemical composition. The NPSEs boast a rich diversity with 138 medicinal plants across 55 families identified as traditionally and pharmacologically used against diabetes globally. Notably, the Asteraceae and Lamiaceae families are prevalent in anti-diabetic applications. In vitro studies reveal their significant inhibition of carbohydrate-metabolizing enzymes, and certain plant co-products regulate genes involved in carbohydrate metabolism and insulin secretion. In vivo trials demonstrate anti-diabetic effects, including glycaemia regulation, insulin secretion, antioxidant activity, and lipid profile modulation. Medicinal plants in NPSE exhibit various activities beyond anti-diabetic, such as antioxidant, anti-inflammatory, antibacterial, anticancer, and more. Chemical analysis identifies over fifty compounds like phenolic acids, flavonoids, terpenoids, and polysaccharides responsible for their efficacy against diabetes. The findings underscore the potential of NPSE medicinal plants as anti-diabetic candidates, urging further research to develop effective plant-based anti-diabetic drugs, beverages, and supplements.
... The hypothesis of PPARγ contribution comes from the observation that the hydroalcoholic extract induces the over-expression of PPARγ and that of the glucose transporter GLUT4 ( Figure 2) in the preadipocytes cell line 3T3-L1. These events could drive the beneficial effect registered for insulin sensitivity in vivo, where this extract at 100 mg/kg i.p. was able to improve the oral glucose and sucrose tolerance tests in a model of chemically induced T2DM (nicotinamide 20 mg/kg i.p. followed by STZ 120 mg/kg i.p.) in CD1 mice [105]. These data highlight the potential insulin-sensitizing action of this plant. ...
... These data highlight the potential insulin-sensitizing action of this plant. Simultaneously, using RINm5F cells, the same authors demonstrated that the hydroethanolic (70% of ethanol) extract of aerial parts of yarrow at 200 μg/mL induced an increase in intracellular Ca 2+ concentration and accordingly of insulin secretion comparable to that of glibenclamide [105]. Consistently, the same study demonstrated, using the OGTT, that yarrow elicits a hypoglycemic response in normoglycemic CD1 mice, thus supporting that it could act as an insulin secretagogue. ...
... Consistently, the same study demonstrated, using the OGTT, that yarrow elicits a hypoglycemic response in normoglycemic CD1 mice, thus supporting that it could act as an insulin secretagogue. However, the possibility of a direct effect on the α-glucosidases was also evaluated in vitro on homogenate of Sprague Dawley rats' intestinal brush border: the yarrow extract inhibited the α-glucosidases activity by 55% [105], confirming previous data [104]. However, the anti-diabetic effects of yarrow could also be ascribed to a more general anti-oxidant potential of the plant observed when exploring the protective effect of a hydroalcoholic extract of yarrow (300 g of plant in 70% ethanol) on lipid profile, blood glucose levels, body weight and serum liver enzymes in a model of T1DM, STZinduced, in rats [192]. ...
Data on urban and rural diabetes prevalence ratios show a significantly lower presence of diabetes in rural areas. Several bioactive compounds of plant origin are known to exert anti-diabetic properties. Interestingly, most of them naturally occur in different plants present in mountainous areas and are linked to traditions of herbal use. This review will aim to evaluate the last 10 years of evidence-based data on the potential anti-diabetic properties of 9 plants used in the Piedmont Alps (North-Western Italy) and identified through an ethnobotanical approach, based on the Occitan language minority of the Cuneo province (Sambucus nigra L., Achillea millefolium L., Cornus mas L., Vaccinium myrtillus L., Fragaria vesca L., Rosa canina L., Rubus idaeus L., Rubus fruticosus/ulmifolius L., Urtica dioica L.), where there is a long history of herbal remedies. The mechanism underlying the anti-hyperglycemic effects and the clinical evidence available are discussed. Overall, this review points to the possible use of these plants as preventive or add-on therapy in treating diabetes. However, studies of a single variety grown in the geographical area, with strict standardization and titration of all the active ingredients, are warranted before applying the WHO strategy 2014–2023.
... The antidiabetic activities of the crude extract and isolated fractions from S. crispus leaves were studied in vitro by testing their ability to inhibit α-glucosidase. α-Glucosidase is a complex enzyme located in the small intestine that hydrolyzes disaccharides such as sucrose and maltose by cleaving the α-(1,4) bond to produce glucose and fructose monosaccharides, which can enter the bloodstream [45]. The inhibition of this enzyme can be applied as a therapy for type 2 diabetes because this inhibition delays or reduces the absorption of carbohydrates [45]. ...
... α-Glucosidase is a complex enzyme located in the small intestine that hydrolyzes disaccharides such as sucrose and maltose by cleaving the α-(1,4) bond to produce glucose and fructose monosaccharides, which can enter the bloodstream [45]. The inhibition of this enzyme can be applied as a therapy for type 2 diabetes because this inhibition delays or reduces the absorption of carbohydrates [45]. Acarbose is used as a reference compound as it is a medicine for treating high glucose levels in type 2 diabetes. ...
A novel green extraction method combining enzymatic and ultrasound-assisted aqueous two-phase extractions was employed to enhance and purify the flavonoid extract from Strobilanthes crispus leaves. Cellulase was used in the pretreatment, and ethanol-(NH4)2SO4 was selected as the solvent. A concentration of 7% (w/w) cellulase and a duration of 2 h were the optimal conditions for pretreatment. The optimal conditions for ultrasound-assisted aqueous two-phase extraction were 33% (w/w) ethanol and 14% (w/w) (NH4)2SO4 as they produced a yield (77.81%), partition coefficient (31.17), extraction efficiency (98.04%), and a high total flavonoid content (0.3666 mg QE/g dry leaf powder). Six compounds from the leaf extract were identified through liquid chromatography-mass spectrometry/mass spectrometry-quadrupole-time of flight (LCMS/MS-Q-TOF) analysis. The crude extract and three compounds in it (kaempferol, graveobioside A, and genistein) showed an antidiabetic activity with IC50 values of 390.35, 201.87, 292.73, and 431.82 mg/mL, respectively. These values are comparable to the standard drug acarbose.
... Regardless of the availability of sufficient insulin preparations and oral hypoglycemic drugs, DM complications remain the most challenging and devastating health problems which affect both adults and children worldwide. Globally, the prevalence of DM for all age groups is estimated at 2.8% in 2000, which is expected to increase to 4.4% by 2030 [4]. In 2017, more than 451 million people (18 -99 years) were lived with DM, and the number was projected to rise to 693 million by 2045 [3,4]. ...
... Globally, the prevalence of DM for all age groups is estimated at 2.8% in 2000, which is expected to increase to 4.4% by 2030 [4]. In 2017, more than 451 million people (18 -99 years) were lived with DM, and the number was projected to rise to 693 million by 2045 [3,4]. ...
Background: In Ethiopian traditional medicine, the leaves of H. abyssinica (Rosaceae) have been used to treat diabetes mellitus. However, the anti-diabetic efficacy of H. abyssinica leaves crude extract has not been properly examined. The goal of this study was to see if the crude extract of H. abyssinica on might prevent diabetes in normoglycemic, oral glucose-loaded, and STZ-induced diabetic mice.
Methods: Successive maceration was used as a method of extraction using solvents of increasing polarity: methanol and water. After extraction of the leaves with 80% hydro methanol, the crude extract was evaluated for its anti diabetic activities using oral glucose loaded, normoglycemic, and single dose-treated diabetic mice model. The extract was evaluated at 100, 200 and 400 mg/kg doses. One-way ANOVA followed by Tukey’s post hoc test was used for data analysis, and p < 0.05 was considered as statistically significant.
Results: The acute toxicity study of H. abyssinica leaf extract did not show mortality in the animals at the limit dose of 2000 mg/kg during the observation period. In normoglycemic model, the percentage reduction of baseline blood glucose level (BGL) was 26.08%, 32.90%, 35.24%, and 53.61% for Hagenia abyssinica crude extract (HAC) 100 mg/kg, HAC 200 mg/kg, 400 mg/kg, and glibenclamide (GLC) 5 mg/kg, respectively when compared to the negative control. The extract at the dose of 200 mg/kg, 400 mg/kg, and GLC treated groups demonstrated significant BGL reduction from peak levels in the OGTT model. In STZ-induced diabetic mice, all doses of the crude extract showed a significant reduction in the fasting BGL. At the 8th hour, the highest percent reductions in blood glucose level (BGL) were recorded in HAC100, HAC200, HAC400 and GL5 with 26.78%, 31.27%, 43.53% and 51.72% reduction respectively compared to their respective baseline fasting BGL levels.
Conclusion: H. abyssinica leaf extract displays antidiabetic activity in normal and STZ-induced diabetic mice, which justifies the claimed traditional use of H. abyssinica in managing DM in Ethiopian folk medicine.
... Licensed Under Creative Commons Attribution CC BY inflammatory and spasmodic), hepatobiliary ailments, as well as overactive cardiovascular and respiratory conditions. [12]. From recent studies done, evidence was found for a substantial decrease in the blood glucose, serum liver enzymes, triglycerides, and total -and LDL -cholesterol levels in the groups using the Achilleamillefolium extract, when compared with the groups not using it. ...
... Hyperglycemia, in patients with DM, is recognized to aggravate the oxidative stress [15]. The Achilleamillefoliumin vivo exerts antidiabetic influence, through multitarget action mechanisms, and involves symptoms of antihyperglycemia (αglucosidases inhibition), hypoglycemia (insulin secretion), and potential insulin sensitizer actions (PPARγ/GLUT4 overexpression) [12]. ...
The metabolic disorder, Diabetes Mellitus (DM), is rapidly growing to be a grave global concern. Despite the development of several synthetic drugs, none of these molecules have been able to effect a total cure. The intake of certain synthetic agents on a continuous basis sometimes results in serious side effects, inducing a persistent demand for non - toxic, inexpensive drugs. Throughout human history, traditional treatments have proven to be highly valued as a medicinal source. From recent studies, herbal extracts have been shown to offer some degree of protection against the diabetes mellitus - related complications. This review discusses some herbal drugs that are effective in the treatment, as well as prevention of complications arising from diabetes.
... A. millefolium is a herbaceous flowering plant that grows wild in Asia, Africa, Europe, and America [33]. In traditional medicine, its extract is widely used to treat inflammatory, hepatobiliary, cardiovascular, and respiratory diseases, as well as diabetes and diabetes-related diseases [34,35]. The main phytochemical compounds isolated from A. millefolium are essential oil and flavonoid derivatives including apigenin, rutin, lutein, and kaempferol [36]. ...
Flavonoids are plant polyphenols that exhibit biological activity with antibacterial, antiviral, antioxidant, anti-inflammatory, antimutagenic, and anticarcinogenic effects. The medicinal plants of Kuzbass have high contents of flavonoids and other polyphenolic compounds. Therefore, they can be used in medicinal preparations to prevent or treat serious diseases. We studied the following plants collected in Kuzbass: common thyme (Thymus vulgaris Linn., leaves and stems), woolly burdock (Arctium tomentosum Mill., roots), alfalfa (Medicago sativa L., leaves and stems), common lungwort (Pulmonaria officinalis L., leaves and stems), common yarrow (Achillea millefolium L., leaves and stems), red clover (Trifolium pratense L., leaves and stems), common ginseng (Panax ginseng, roots), sweetvetch (Hedysarum neglectum Ledeb., roots), and cow parsnip (Heracleum sibiricum L., inflorescences, leaves, and stems). To extract flavonoids, we used ethanol at concentrations of 40, 55, 60, 70, and 75%. Spectrophotometry was used to determine total flavonoids, while high-performance liquid chromatography was employed to study the qualitative and quantitative composition of the extracts. The highest yield of flavonoids was found in H. sibiricum leaves (at all concentrations except 70%), followed by the 55% and 70% ethanol extracts of T. vulgaris leaves and stems, as well as the 75% ethanol extract of A. millefolium leaves and stems. Thus, these plants have the greatest potential in being used in medicines. High-performance liquid chromatography showed the highest contents of polyphenolic compounds in the samples of P. officinalis, A. millefolium, T. vulgaris, and T. pratense. Our results can be used in further research to produce new medicinal preparations based on the medicinal plants of Kuzbass.
... Our study aimed to determine the potential antidiabetic effect of Achillea spp., a medicinal plant used in the treatment of various diseases, including diabetes, in Türkiye and Cyprus. These plants exert their antidiabetic effects by controlling hyperglycaemia through the inhibition of enzymes such as α-amylase and α-glucosidase, as well as delaying glucose absorption [14,15]. Acarbose was used as a standard, and it was found to have a strong inhibitory activity against α-amylase and α-glucosidase when compared to ZnO-NPs/Ach. ...
... Moreover, South American ethnopharmacobotany documents its antidiabetic and anti-hypercholesterinemic effects [120]. The hydroalcoholic extract of the plant presented an in vivo antidiabetic effect through α-glucosidase and lipase inhibition, insulin secretion enhancer, and potential insulin sensitizer through PPARγ/GLUT4 overexpression stimulation [121]. Many studies have found that the herbs previously mentioned could interact with antidiabetic medications, often resulting in an enhanced effect. ...
Diabetes mellitus affects carbohydrate homeostasis but also influences fat and protein metabolism. Due to ophthalmic complications, it is a leading cause of blindness worldwide. The molecular pathology reveals that nuclear factor kappa B (NFκB) has a central role in the progression of diabetic retinopathy, sharing this signaling pathway with another major retinal disorder, glaucoma. Therefore, new therapeutic approaches can be elaborated to decelerate the ever-emerging “epidemics” of diabetic retinopathy and glaucoma targeting this critical node. In our review, we emphasize the role of an improvement of lifestyle in its prevention as well as the use of phytomedicals associated with evidence-based protocols. A balanced personalized therapy requires an integrative approach to be more successful for prevention and early treatment.
... It can cause neutropenia or a lack of macrophages, which are important players in innate immunity [34][35][36] . PHZ, the anemia inducer, could cause cardiac cytopenia [38][39] . And PTK787 is a novel tyrosinase inhibitor that affects the anatomy of the tumor vascular bed and the functional vascular properties [40][41] . ...
Fufang E’jiao Jiang (FEJ) as a healthy food consisting of medicine food homology materials approved by China’s Ministry of Health has been extensively applied to replenish qi and nourish blood, and it has a positive impact on women’s health. To find out the material basis and mechanism of FEJ, a systematic “compound-effect-target” analysis including chemical composition resolution, zebrafish, network pharmacology, molecular docking, transcriptome, and bibliometric analysis was adopted. 124 chemical components including ginsenosides, and phenylethanoid glycosides in FEJ were discovered, and effects of FEJ on promoting the generation of immune cells, erythropoiesis and angiogenesis in zebrafish were exhibited. Based on network pharmacology, molecular docking and in vivo activity assay, 6 compounds including jionoside A1, isoacteoside, echinacoside, acteoside, lobetyolin, and rehmannioside D were identified as active components of FEJ. Transcriptome data showed that several pathways such as complement and coagulation cascades, ECM-receptor interaction, and PI3K-Akt signaling pathway were associated with proangiogenic effect of FEJ. 19 common targets were obtained through combined analysis of network pharmacology and transcriptomics, and 5 targets of them were verified by PCR. The bibliometric analysis of these common targets revealed that FEJ was related to energy metabolism, pathway in cancer, etc., which was consistent with the results of network pharmacology and transcriptome. The studies suggested that FEJ could replenish qi and nourish blood through multi-compound and multi-targets.
... The genus has nineteen species in Iran, of which seven are endemic and are usually grown as wild populations in various places (Mozaffarian, 2003;Rechinger, 1978). Some Achillea species have ethnopharmacological importance and are well known for their anthelmintic, anti-inflammatory, antispasmodic, diaphoretic, diuretic, and antimicrobial properties (Achakzai et al., 2019;Arias-Durán et al., 2020, 2021Chávez-Silva et al., 2018). In Iranian folk medicine, the aerial parts of some Achillea species, particularly the inflorescences, have been used to treat fever, asthma, bronchitis, cough, skin irritation, digestive system disorders, cardiac failure, jaundice, and other liver (Ghorbani, 2005;Marrelli, 2021;Saeidnia et al., 2009). ...
Yarrow species (Achillea L.) have therapeutic importance, and due to the wide distribution of diverse species of the genus in Iran, in the present study, the seed oil content and fatty acid (FA) composition of seven populations from five species were examined and analyzed from chemotaxonomic and nutritional standpoints. The taxonomic status of the infra-generic grouping of the genus was identified using numerical analysis. UPGMA (Unweighted Pair Group Method with Arithmetic Mean) clustering was determined based on the Euclidean similarity index to evaluate the possibility of grouping the studied populations. A detailed examination of the data indicated that the total oil content of the seeds ranged from 25.25 to 30.22% dry weight. Linoleic (46.74–74.19%), oleic (18.14–37.39%), palmitic (5.48–11.48%), and stearic (1.07–3.84%) acids were the most prevalent in the species. The n-6 FA content varied from 47.35 to 74.80%. Our results showed that FA signatures might be used as reliable chemotaxonomic strategies to distinguish Achillea species at the inter-sectional level. A fatty acid study revealed that the seed oils of various Achillea species might be employed as potential sources of novel n-6 polyunsaturated fatty acids in foods, cosmetics, and pharmaceutical preparations.
... The HAEPa effect on PPARγ and GLUT4 expression was determined in fibroblasts 3T3-L1 according to Chávez-Silva et al. [54]. The 3T3-L1 cells (~80% confluence) were differentiated to the adipocyte phenotype with a mix for differentiation (0.5 µM 3-isobutyl-1-methylxanthine, 0.25 µM dexamethasone acetate, and 0.8 µM insulin for 48 h), followed by insulin for 48 h more. ...
Plantago australis Lam. Subsp. hirtella (Kunth) Rahn is a medicinal plant used as a diuretic, anti-inflammatory, antibacterial, throat cancer treatment and for the control of diabetes. P. australis was collected in the state of Morelos, México. The hydroalcoholic extract (HAEPa) of P. australis was obtained by maceration and concentrated in vacuo. Once dry, it was evaluated through an oral glucose tolerance test (OGTT) in normoglycemic mice and in a non-insulin-dependent diabetic mice model. The expression of PPARγ and GLUT-4 mRNA was determined by rt-PCR, and GLUT-4 translocation was confirmed by confocal microscopy. The toxicological studies were conducted in accordance with the guidelines suggested by the OECD, sections 423 and 407, with some modifications. HAEPa significantly decreased glycemia in OGTT curves, as well as in the experimental diabetes model compared to the vehicle group. In vitro tests showed that HAEPa induced an α-glucosidase inhibition and increased PPARγ and GLUT-4 expression in cell culture. The LD50 of HAEPa was greater than 2000 mg/kg, and sub-chronic toxicity studies revealed that 100 mg/kg/day for 28 days did not generate toxicity. Finally, LC-MS analysis led to the identification of verbascoside, caffeic acid and geniposidic acid, and phytochemical approaches allowed for the isolation of ursolic acid, which showed significant PPARγ overexpression and augmented GLUT-4 translocation. In conclusion, HAEPa induced significant antidiabetic action by insulin sensitization through PPARγ/GLUT-4 overexpression.
... Achillea millefolium commonly known as yarrow plant belongs to Asteraceae family and is traditionally used in the mitigation of cuts, abrasions, wounds and ulcers [59][60][61][62]. It has been established that the plant contains volatile oils. ...
Wound healing is a process through which skin maintains itself. Once a wound occurs, the inflammatory and proliferative stages are instigated in reaction to injury. It is established that wound restorative comprises four stages including haemostasis, inflammation, proliferation, and remodeling. The amelioration of wound healing is very challenging as tumors can develop at the site of chronic injury. There are numerous plants, plant extracts and plant based natural products were widely used by tribal communities from ancient times for the treatment of cuts, burns, scars, burns and wounds. The therapeutic potential of these plants is recognized due to the presence of phytomolecules such as phenolic compounds, flavonoids, triterpenoids, saponins, tannins, alkaloids and glycosides. The plant used for the treatments of wound healing includes Achillea millefolium, Andrographis paniculata, Boswellia sacra, Calendula officinalis, Crocus sativus, Curcuma longa, Ehretia laevis, Ehretia microphylla, Glycyrrhiza glabra, Malva sylvestris, Rosmarinus officinalis and Salvia officinalis. This assemblage comprises the structures of phytomolecules isolated from the different extracts of these plants, mechanistic insights and important key findings responsible for wound healing. The mechanistic insights involved in wound healing are similar to cytotoxic, anti-inflammatory and antioxidant agents such as ROS generation, DNA fragmentation and western blotting. This review article is an effort to bridge the gaps in the prevailing literature and thus offers gigantic scope for researchers and academicians betrothed in validation of the customary claims and development of safer and efficient and worldwide recognized natural potential candidates as drugs for healing of wounds, burns and cuts.
... It has been shown that Achillea contains bitter aromatic substances having imperative effects on nervous system and neurological diseases such as epilepsy, neurasthenia, and seizures [9]. Many research studies documented that fractions, extracts, pure chemical compounds, and essential oils derived from Achillea species have a wide range of biological functions such as cytotoxic, antidiabetic, antispasmodic, antianxiety, anticancer, anti-inflammatory, analgesic, antibacterial, anticholinesterase activities [10,11]. The plant decoction is used to treat children's motion, jaundice stomach pain, and fever, whereas green tea made from young shoots is used to treat stomach complications [12]. ...
Medicinal plants are rich source of phytochemical constitutes and can be used to treat many human diseases. Infectious diseases have always been a major source of concern. Globally, the medicinal plant Achillea wilhelmsii locally known as Bohe Madran is extensively dispersed and widely used as traditional medicine. The aim of this present work is to investigate phytochemical constituents and antimicrobial, antioxidant, and anti-inflammatory properties of the whole plant ethanolic extract of Achillea santolinoides subsp. wilhelmsii (WEEAW) from Balochistan region. The total phenolic content was 14.81 ± 0.18 mg GAE/g of the extract whereas the total flavonoid content was 12.27 ± 0.12 mg QE/g of the extract. The antioxidant ability of the extract was analyzed by DPPH (2,2-diphenyl-1-picryl-hydrazyl) scavenging assay and FRAP (ferric reducing antioxidant power) assay in terms of concentration having 50% inhibition (IC50). Results showed that IC50 value for DPPH% inhibition was 0.367 ± 0.82 mg/mL while FRAP assay represented with IC50 value of 0.485 ± 1.26 mg/mL. In antileishmanial bioassay, the extract was analyzed against Leishmania major and showed good activity with IC50 value of 7.02 ± 0.83 mg/mL. Antibacterial assay revealed that Staphylococcus aureus was highly sensitive with the diameter of inhibition zone ( 21.61 ± 1.09 mm) followed by Salmonella typhi ( 17.32 ± 0.15 mm), Pseudomonas aeruginosa ( 16.41 ± 0.63 mm), and Escherichia coli ( 15.30 ± 1.17 mm) while Klebsiella pneumoniae showed minimum inhibition ( 14.13 ± 0.49 mm). Antifungal activity was tested against Aspergillus flavus with 89% of inhibition zone and 77% against Mucor mucedo and Aspergillus niger with 74% of inhibition zone. The anti-inflammatory assay was carried out by inhibiting protein denaturation, proteinase inhibitory activity, and heat-induced hemolysis. The IC50 value for protein denaturation was 6.67 ± 1.25 mg/mL, proteinase inhibitory with IC50 value of 4.12 ± 0.69 mg/mL, and heat-induced hemolysis assay with IC50 value 4.53 ± 0.82 mg/mL by comparing to the standard drug aspirin having IC50 value 1.85 ± 0.54 mg/mL. Results of the current work showed that whole plant ethanolic extract of Achillea wilhelmsii exhibited substantial anti-inflammatory action, thus can be utilized as a traditional treatment. Furthermore, overall finding of this research suggested that the antioxidant potential of the plant aids to prevent free radical damage and reduce the incidence of chronic disease. More research is needed to find out more active compounds present in the extract that are responsible for their pharmacological effects.
... In the data corresponding to glucose values, a signi cant decrease was also observed in the Achillea, Matricaria and Rosmarinus groups compared to the control group (p < 0.05). This hypoglycemic effect has been detected by other authors [12,13,14]. ...
Plant extracts can be an important adjuvant treatment in gastrointestinal diseases where intestinal transit is involved. Because transit disorders are often associated with infections and inflammation, in our investigation we have selected five aromatic Mediterranean plants with antimicrobial, antioxidant and anti-inflammatory activities which in certain areas are also used for culinary reasons. We evaluated the intestinal transit in mice after oral administration of hydro-alcoholic extracts of Achillea millefolium L. Sideritis angustifolia Lag., Rosmarinus officinalis L. Matricaria chamomile L., and Aloysia citriodora Palau.
Total content of phenols and flavonoids and their antioxidant activity were previously determined. Rosmarinus officinalis showed the highest antioxidant capacity (p < 0.001) in the DPPH and ABTS methods with IC50 of 48.89 ± 2.98 and 27.28 ± 1.83 µg/mL respectively, in agreement with the highest phenol content.
Oral administration of the extracts to mice and rats showed no signs or symptoms of toxicity in any case. The extracts of A. millefolium, R. officinalis, and M. chamomilla significantly inhibited intestinal transit (p < 0.01 and p < 0.05) when compared to the castor oil control group, with a percentage of intestinal transit similar to that of the reference antidiarrheal loperamide drug (47.8 ± 3.6%).
These non-toxic plant extracts constitute a valuable basis to produce dietary supplements for intestinal motility disorders.
... Achillea millefolium L. (yarrow) is an important species of Asteraceae family with common utilization in the traditional medicine of several cultures from Europe to Asia for the treatment of various disorders including wounds, cuts, abrasions, and diabetic ulcers [52][53][54][55]. Essential oils, the most active part of the yarrow flower, are used in wound therapy as a hemostatic [56][57][58]. ...
Wound healing is a complicated process, and the effective management of wounds is a major challenge. Natural herbal remedies have now become fundamental for the management of skin disorders and the treatment of skin infections due to the side effects of modern medicine and lower price for herbal products. The aim of the present study is to summarize the most recent in vitro, in vivo, and clinical studies on major herbal preparations, their phytochemical constituents, and new formulations for wound management. Research reveals that several herbal medicaments have marked activity in the management of wounds and that this activity is ascribed to flavonoids, alkaloids, saponins, and phenolic compounds. These phytochemicals can act at different stages of the process by means of various mechanisms, including anti-inflammatory, antimicrobial, antioxidant, collagen synthesis stimulating, cell proliferation, and angiogenic effects. The application of natural compounds using nanotechnology systems may provide significant improvement in the efficacy of wound treatments. Increasing the clinical use of these therapies would require safety assessment in clinical trials.
... The dark blue essential oil is obtained from its flowers and often used as an anti-inflammatory or chest rub for colds and influenza. The leaves encourage clotting so it can be used fresh for nosebleeds (Choudhary et al., 2007;Lakshmi et al., 2011;Ali et al., 2017;Chávez-Silva et al., 2018). ...
... The antidiabetic effect of the hydroalcoholic extract of aerial parts of Achillea millefolium was evaluated by Chávez-Silva et al. [33]. The extract showed α-glucosidases inhibition by 55% at 1 mg/ml relative to control. ...
The beneficial effect of plants in treating diabetes is not only well-known in traditional medicine but also confirmed in numerous scientific studies. The basic platform for testing the potential antidiabetic activity of traditionally known plants and their bioactive compounds is a set of in vitro, in vivo experiments, clinical trials and molecular docking studies. Basic assays usually measure enzyme inhibitory activity (α-amylase and α-glucosidase) and other aspects related to diabetes mellitus disease. Recently, the use of plant-derived compounds has proven useful in treating diabetes and reducing complications resulting from high blood sugar levels. The main goal is to establish an action mechanism of plant extracts or active compounds to find new antidiabetic drugs with less toxicological properties. This work aims to collect data and discuss the newest results in the area of plant extracts, compounds and antidiabetic effects using in vitro, in vivo and in silico models. The data covered in this review include plant extracts, polyphenols, terpenoids, saponins, phytosterols, and other bioactive compounds, with some of the investigated plants being less known. Isolation of new compounds might be a plentiful source for treatment and prevention of diabetes mellitus. Clinical trials with adequate monitoring give the best results of plants' product efficacy and safety. Many studies give us the confirmation for importance of patent and use medicinal herbs in the treatment of diabetes.
... for EAQ 200 mg/kg and P<0.001 for EAF 400 mg/kg) and at 120 min (P<0.01 for EAF 400 mg/kg) post-oral glucose loading. These findings showed that the improvement in glucose tolerance by the solvent fractions may be because of insulin-sensitizing effect of H. abyssinica possibly through peroxisome proliferator-activated receptor-gamma activation or simulation of β-cells of the pancreas to release insulin leading to increased glucose utilization by peripheral tissues [50,51]. The mechanism involved in decreased postprandial hyperglycemia is inhibition of enzymes like α-amylase and α-glycosidase in the gastrointestinal system which avoids postprandial hyperglycemia [52,53]. ...
Background:
Hagenia abyssinica leaves have been used traditionally for the management of different diseases including diabetes mellitus (DM) although the antidiabetic effect of different solvent fractions of hydromethanol H. abyssinica leaf extract has not been scientifically studied. Thus, this study was conducted to investigate the in vivo hypoglycemic, antihyperglycemic and antidyslipidemic effects of the solvent fractions of Hagenia abyssinica leaf extract.
Methods:
The antidiabetic effect of the solvent fractions was evaluated in normal, oral glucose loaded and streptozotocin-induced diabetic mice. Hypoglycemic, antihyperglycemic, antidyslipidemic activities and effect on body weight change were evaluated after administration of three different doses of the solvent fractions (100, 200, and 400 mg/kg). One-way ANOVA followed by Tukey's post hoc test was used for data analysis, and p<0.05 was considered as statistically significant.
Results:
The crude hydromethanol extract of H. abyssinica leaves did not show any sign of toxicity at the dose of 2000 mg/kg in mice. In normoglycemic mice, both aqueous and ethyl acetate fractions of H. abyssinica leaves showed significant (P<0.05) hypoglycemic activity. In oral glucose loaded mice, the two doses of the aqueous fraction, 200 mg/kg (p<0.05) and 400 mg/kg (p<0.001), showed a significant antihyperglycemic effect at 60 and 120 minute post-oral glucose loading while the ethyl acetate fraction showed significant antihyperglycemic effect at 60 (P<0.05 for 200 mg/kg and P<0.001 for 400 mg/kg) and 120 min (P<0.01 for 400 mg/kg) post-oral glucose loading. In single dose-treated diabetic mice, all doses of the solvent fractions caused a significant (P<0.05) reduction in blood glucose level except 100 mg/kg of the aqueous and chloroform fractions. Additionally, repeated daily treatment with the aqueous fraction significantly reduced hyperglycemia, body weight loss, and improved dyslipidemia of diabetic mice.
Conclusion:
This study has revealed that the solvent fractions of H. abyssinica leaves possess in vivo blood-glucose-lowering activities on normal, oral glucose loaded, and streptozotocin-induced diabetic mice. Additionally, the aqueous fraction prevented diabetic body weight loss and dyslipidemia in mice after repeated daily dose administration.
... Many biological and pharmaceutical properties of Achillea species have been revealed by scientific studies over time. Some of these features are anti-inflammatory [11], antinociceptive [12], antifungal [13], antibacterial [14], antimicrobial [15], antioxidant [16], antidiabetic [17], wound healer [18] and anticancer [19,20]. The phytochemical studies have shown that Achillea species have rich secondary metabolite content. ...
Background
In the treatment of colorectal cancer (CRC), the search for new antineoplastic drugs with fewer side effects and more effectiveness continues. A significant part of these pursuits and efforts focus on medicinal herbs and plant components derived from these plants. A. ketenoglui is one of these medicinal plants, and its anticancer potential has never been studied before.
Methods
The phenolic and flavonoid content, and antioxidant activity of A. ketenoglui extracts were determined. The phytochemical profiling and quantification analysis of major components were performed by HPLC-ESI-Q-TOF-MS. Cytotoxicity, proliferation, apoptosis and cell cycle were evaluated to reveal the anticancer activity of the extract on CRC cells (HCT 116 and HT-29). The determined anticancer activity was confirmed by mRNA (RT-qPCR) and protein (Western blotting) analyzes.
Results
A. ketenoglui methanol extract was found to have high phenolic (281.89±0.23) and flavonoid (33.80±0.15) content and antioxidant activity (IC50 40.03±0.38). According to the XTT assay, the extract has strong cytotoxic activity (IC50 350 µM in HCT 116 and IC50 263 µM in HT-29 cell line). The compounds most commonly found in the plant are, in descending order, chlorogenic acid, apigenin, genistin, baicalin, eupatorin, casticin, and luteolin. In flowcytometric analysis, the extract was found to induce greater apoptosis and cell cycle arrest in both cell lines than in both control and positive control (casticin). According to the results of the mRNA expression analysis, the extract treatment upregulated the expression of the critical genes of the cell cycle and apoptosis, such as p53, p21, caspase-3, and caspase-9. In protein expression analysis, an increase in caspase-3 and p53 expression was observed in both cell lines treated with the extract. In addition, caspase-9 expression was increased in HT-29 cells.
Conclusion
The findings show that A. ketenoglui has an anticancer potential by inducing apoptosis and arresting the cancer cell cycle and may be promising for CRC therapy. This potential of the plant is realized through the synergistic effects of its newly identified components.
... Achillea millefolium L. (Asteraceae) is a very important medicinal plant of traditional medicine to treat headaches, hepatobiliary disorder, gastrointestinal complaints and inflammations, wounds, cuts, abrasions, cardiovascular diseases and diabetes (Cavalcanti et al., 2006;Benedek and Kopp, 2007;Chávez-Silva et al., 2018;Ali et al., 2017;Monroy-Ortiz and Castillo-España, 2007). It is important to mention that the Pharmacopoeia of the Russian Federation refers to the infusion of aerial parts of A. millefollium (15 g in 200 mL), 2-3 times a day as a hemostatic, anti-inflammatory and sedative (Shikov et al., 2017(Shikov et al., , 2021. ...
Ethnopharmacological relevance
Achillea millefolium L. (Asteraceae), known as yarrow (milenrama), is a plant used in Mexican traditional medicine for the treatment of hypertension, diabetes, and related diseases.
Aim
To determine the vasorelaxant and antihypertensive effect of A. millefollium and to isolate the main bioactive antihypertensive agents.
Materials and Methods
Organic (hexane, dichloromethane and methanol) and hydro-alcohol (Ethanol-H2O: 70:30) extracts obtained from flowers, leaves and stems were evaluated on isolated aorta rat rings with and without endothelium to determine their vasorelaxant effect. Hexane extract from flowers (HEAmF) was studied to evaluate its antihypertensive effect on spontaneously hypertensive rats (SHR). From HEAmF, bioactive compounds were obtained by bio-guided phytochemical separation through chromatography.
Results
Organic extracts showed the best vasorelaxant activity. Hexane extract from flowers was the most potent and efficient ex vivo vasorelaxant agent, showing significant decrease of systolic and diastolic blood pressure in SHR (p<0.05). Phytochemical separation of HEAmF yielded two epimeric sesquiterpene lactones: leucodin (1) and achillin (2), the major components of the extract. Both 1 and 2 showed similar vasorelaxant action ex vivo (p<0.05), and their effects where modified by L-NAME (10 μM, nitric oxide synthase inhibitor), by ODQ (1 μM, soluble guanylyl cyclase inhibitor), and also relaxed the contraction induced by KCl (80 mM). Finally, 1 and 2 intragastric administration (50 mg/kg) decreased systolic and diastolic blood pressure in SHR.
Conclusions
Achillea millefolium showed antihypertensive and vasorelaxant effects, due mainly to leucodin and achillin (epimers). Both compounds showed antihypertensive activity by vasorelaxation putatively by endothelium-dependent NO release and cGMP increase, as well as by calcium channels blockade.
... To identify part of the probable mechanism by which the plant exerts its activity, inhibition of α-glucosidases (with sucrose and starch) or the glucose transport mechanism (glucose), studies were conducted consistent with other plants species from diverse families, such as Calea ternifolia [9], Annona cherimolla [10], or Scutellaria baicalensis [11], for example, that had been studied as antihyperglycemic agents [8][9][10][11][12][13]. The OTT technique was performed after an overnight fasting (18 h) of normoglycemic mice. ...
Salvia amarissima Ortega was evaluated to determinate its antihyperglycemic and lipid profile properties. Petroleum ether extract of fresh aerial parts of S. amarissima (PEfAPSa) and a secondary fraction (F6Sa) were evaluated to determine their antihyperglycemic activity in streptozo-cin-induced diabetic (STID) mice, in oral tolerance tests of sucrose, starch, and glucose (OSTT, OStTT, and OGTT, respectively), in terms of glycated hemoglobin (HbA1c), triglycerides (TG), and high-density lipoprotein (HDL). In acute assays at doses of 50 mg/kg body weight (b.w.), PEfAPSa and F6Sa showed a reduction in hyperglycemia in STID mice, at the first and fifth hour after of treatment, respectively, and were comparable with acarbose. In the sub-chronic test, PEfAPSa and F6Sa showed a reduction of glycemia since the first week, and the effect was greater than that of the acarbose control group. In relation to HbA1c, the treatments prevented the increase in HbA1c. In the case of TG and HDL, PEfAPSa and F6Sa showed a reduction in TG and an HDL increase from the second week. OSTT and OStTT showed that PEfAPSa and F6Sa significantly lowered the postprandial peak at 1 h after loading but only in sucrose or starch such as acarbose. The results suggest that S. amarissima activity may be mediated by the inhibition of disaccharide hydrolysis, which may be associated with an α-glucosidase inhibitory effect.
... The antidiabetic activity of natural extracts has been widely reported [12,16,41,42]. This property has been attributed mainly to the content of polyphenols and associated chemical families such as flavonoids and hydroxycinnamic acids. ...
Cactus acid fruit (Xoconostle) has been studied due its content of bioactive compounds. Traditional Mexican medicine attributes hypoglycemic, hypocholesterolemic, anti-inflammatory, antiulcerogenic and immunostimulant properties among others. The bioactive compounds contained in xoconostle have shown their ability to inhibit digestive enzymes such as α-amylase and α-glucosidase. Unfortunately, polyphenols and antioxidants in general are molecules susceptible to degradation due to storage conditions, (temperature, oxygen and light) or the gastrointestinal tract, which limits its activity and compromises its potential beneficial effect on health. The objectives of this work were to evaluate the stability, antioxidant and antidiabetic activity of encapsulated extract of xoconostle within double emulsions (water-in-oil-in-water) during storage conditions and simulated digestion. Total phenols, flavonoids, betalains, antioxidant activity, α-amylase and α-glucosidase inhibition were measured before and after the preparation of double emulsions and during the simulation of digestion. The ED40% (treatment with 40% of xoconostle extract) treatment showed the highest percentage of inhibition of α-glucosidase in all phases of digestion. The inhibitory activity of α-amylase and α-glucosidase related to antidiabetic activity was higher in microencapsulated extracts than the non-encapsulated extracts. These results confirm the viability of encapsulation systems based on double emulsions to encapsulate and protect natural antidiabetic compounds.
In this study, Lactic acid bacteria were isolated from traditional fermented foods in Guizhou. The fermentation supernatant and cell disruption extract were used to screen Lactic acid bacteria with α-glucosidase inhibitory activity, and the active Lactic acid bacteria strains with potential hypoglycemic effect were screened. The results showed that 10 strains were screened from 27 strains of Lactic acid bacteria with α-glucosidase inhibitory activity, of which 5 strains had good acid and bile salt tolerance. The best acid resistance was XG01, and the survival rate was as high as 98.5%. ST01 had the strongest tolerance to bile salt, up to 77.3%. Through molecular biological identification, HLG01, YR01, and ST01 were Lactiplantibacillus plantarum , XG01 was Pediococcus pentosaceus , and JR01 was Weissella cibaria . Five strains of Lactic acid bacteria with good tolerance were screened out, which provided a strain basis for the subsequent study of the hypoglycemic effect of Lactic acid bacteria and the development of various functional foods.
Herbal therapy is the most common modality of alternative and complementary treatment, mainly based on the thought that all herbs are safe as “natural.” On the other hand, scientists are becoming more interested in herbs as useful therapeutic tools in a number of diseases, in particular in gastroenterology. Thus, the debate on the efficacy, safety, and quality of herbal or natural products has increased interest, based on a number of evidence on the pharmacodynamic/pharmacokinetic pathways underlying herb-drug interactions and their effects on health. An adequate understanding of these mechanisms is essential for minimizing clinical risks but also for ameliorating the efficacy of both drugs and herbs, particularly in the case of polytherapy, a mixture of different herbs and in subjects with chronic diseases.
Diabetes Mellitus is a metabolic disorder characterized by high blood glucose levels, causing significant morbidity and mortality rates. This study investigated the antidiabetic, neuroprotective, and antioxidant effects of ethanol extracts of Parkia biglobosa (PB) leaves and seeds in streptozotocin (STZ)-induced diabetic rats. The administration of STZ significantly elevated fasting blood glucose levels (FBGL) to 355–400 mg/mL compared to 111 mg/mL in normal controls, indicating hyperglycemia. Treatment with PB extracts at 100 mg/kg and 200 mg/kg significantly (p < 0.05) reduced FBGL in a dose-dependent manner. No significant difference was observed between the effects of metformin and PB extracts at 200 mg/kg. Cognitive dysfunction, assessed using the Y-maze test, was significantly improved in groups treated with PB extracts (p < 0.05), particularly at 200 mg/kg, through inhibition of cholinesterase activity and protection against oxidative damage. Both PB extracts also demonstrated significant inhibition (p < 0.05) of α-amylase and α-glucosidase activity, reducing postprandial hyperglycemia, with a stronger inhibition at 200 mg/kg. Additionally, PB extracts significantly increased catalase (CAT) and superoxide dismutase (SOD) activities, reversing the diabetes-induced decline in antioxidant enzyme levels. Monoamine oxidase (MAO) activity, elevated in diabetic conditions, was significantly downregulated by PB treatment, further contributing to neuroprotection. The neuroprotective effects may be attributed to the inhibition of cholinesterase and MAO, which help maintain neurotransmitter levels, alongside the antioxidant properties that mitigate oxidative stress in the brain. These findings suggest that PB extracts could serve as a natural therapeutic agent for diabetes management, with its effects comparable to metformin at higher doses.
In the pursuit of effective diabetes management, inhibiting α-amylase activity stands as a critical strategy. This inhibition regulates post-meal blood sugar levels by retarding carbohydrate digestion, mitigating abrupt glucose spikes, and enhancing glycemic control, thus safeguarding against diabetic complications. In this study, molecular docking and DFT investigations were conducted on phytochemical compounds sourced from various plants, unveiling Conanine, Friedelin, Sennoside A, and Sennoside B as promising candidates. These compounds demonstrated robust binding affinities exceeding-9 kcal/mol when targeted against α-amylase, with Conanine leading the charge at-9.5 kcal/mol. Sennoside A and Sennoside B exhibited their effectiveness by forming multiple hydrogen bonds with the enzyme, underlining their strong binding interactions. Furthermore, DFT calculations affirmed the favorable chemical reactivity profiles of these ligands, characterized by significant HOMO-LUMO energy gaps. This research offers valuable insights into potential therapeutic agents for diabetes management, promising better glycemic control and a brighter future for individuals with diabetes.
Diabetes mellitus is a metabolic disorder that can lead to various complications affecting the heart, kidney, and eye. Several synthetic and natural products have been used for disease management, but the disease still remains a global challenge. The use of plants as an alternative management for diabetes has been on the rise. Regrettably, the comprehensive repository is not available to guide future research in the area of plants with a related mechanism of action for the development of an effective drug. To identify and compile medicinal plants frequently used with proven scientific hypoglycaemic properties and their possible modes of action. This was done through a literature search of scientific databases using search tools like DOAJ, EMBASE, Europe PMC, FSTA, Google Scholar, HubMed, Indian Citation Index, Medline Plus, Merck Index, PubMed, ScienceDirect, Science3open, Science Open, SciFinder, Scirus, Core, Scopus, Semantic Scholar, Shodhganga, and World Wide Science. Search keywords included: medicinal plants, antidiabetics, hypoglycaemic, alpha-amylases/glucosidase inhibition, glucose metabolic enzymes, antihyperglycaemia, insulin secretion/surrogate, β-cell amelioration, phytochemicals, diabetes management, anti-oxidant, and enhance glucose transporters. The study excludes plants used in the management of diseases other than diabetes mellitus. From the search, 611 authenticated medicinal plants with anti-diabetic properties were eligible and grouped according to their reported probable mode of action. Precisely 20.6% of the plants exhibited their anti-diabetic effect via prevention of oxidative stress; 11.6% acted through stimulation of insulin secretion, inhibition of insulin degradation, and reduction of insulin resistance. Also, 10.8% inhibited enzymes of carbohydrate gastrointestinal digestion, 2.8% were postulated to regulate enzymes of glucose metabolism, and 54.2% acted via nonspecific or multiple means, as well as those whose anti-diabetic mode of action was yet to be identified. This study has shown that the exact mechanisms or mode of action of the majority of plants with hypoglycaemic properties are yet to be explored. Scientists would therefore find this paper useful in their future research. This paper may also serve as a potential lead for the easy harmonization of plants with a related mode of action in the drug discovery process targeted at the management of diabetes mellitus.
Graphical abstract
In the pursuit of effective diabetes management, inhibiting α-amylase activity stands as a critical strategy. This inhibition regulates post-meal blood sugar levels by retarding carbohydrate digestion, mitigating abrupt glucose spikes, and enhancing glycemic control, thus safeguarding against diabetic complications. In this study, molecular docking and DFT investigations were conducted on phytochemical compounds sourced from various plants, unveiling Conanine, Friedelin, Sennoside A, and Sennoside B as promising candidates. These compounds demonstrated robust binding affinities exceeding -9 kcal/mol when targeted against α-amylase, with Conanine leading the charge at -9.5 kcal/mol. Sennoside A and Sennoside B exhibited their effectiveness by forming multiple hydrogen bonds with the enzyme, underlining their strong binding interactions. Furthermore, DFT calculations affirmed the favorable chemical reactivity profiles of these ligands, characterized by significant HOMO-LUMO energy gaps. This research offers valuable insights into potential therapeutic agents for diabetes management, promising better glycemic control and a brighter future for individuals with diabetes.
Natural products contain diverse bioactive compounds with therapeutic and pharmacological potential, including antimicrobial, antioxidant, anticancer, antifungal properties, and respiratory benefits for conditions. Bioactive volatile organic compounds were identified using headspace-gas chromatography in Curcuma longa L (CL). and Curcuma caesia Roxb. (CC) leaves, with CL leaves containing 90.48% terpenes and CC leaves containing 77.5% terpenes and 22.5% non-terpenes. The total phenolic content and antioxidant capacity were evaluated, employing a 2x7 factorial design analyzed through one-way and factorial ANOVA. Methanol:water and ethanol extracts from CL exhibited superior radical sequestering capacity (IC50 of 0.35 mg mL-1) compared to CC extracts. The highest Ferric Reducing Antioxidant Power value of 95.28 µMol FeSO g-1 was achieved analyzing methanol:water. Ethanol:water was considered most appropriate, as it is the most suitable solvents for industrial food processing due to safety and compatibility aspects.
A multicomponent-derived synthesis of arylidene isoquinolinones decorated with phenolic moieties is described. The series demonstrated good DPPH trapping and, in the case sinapic-containing analogs, excellent activity against lipoperoxidation; EPR also...
Background
Achillea millefolium, known as Yarrow, is a medicinal plant in the Asteraceae family which is one of the oldest known botanicals used by humans and itis one of the most important medicinal plants in the pharmaceutical field. Purpose: This review discusses pharmacodynamics, pharmacokinetics, and mechanism of action of the most important component of Achillea millefolium. There are a variety of same species such as white, red and yellow yarrow and all of these species have been discussed in this manuscript. We focus on previously discovered hormonal, antibiotic, and anticancer drug interactions with Achillea millefolium that may decrease or increase the concentration of certain drugs. We categorized different interactions of this herb into minor and serious ones, such as affecting Cytochromes P450 metabolism enzyme, resulting in a concentration rise in drugs such as Erythromycin, Diazepam, and Cyclosporine.
The reason of writing a review article in this field is our enthusiasm for pharmacology of herbal ingredients and also, we want to gather other scientists’ and our knowledge in this review for future researchers who like to know more about this plant pharmacological criteria in order to make their way.
Method
Pharmacological and phytochemical-specific details of Achillea millefolium, as well as related keywords, were used to conduct a literature search across the following essential collections of electronic databases: Web of Science, Google Scholar, PubMed, and Science Direct.
Outcome
Achillea millefolium medical indications are the treatment of spasmodic gastrointestinal ulcers, inflammation, wound healing, and cancers, as well as excellent antioxidant activity. Camphene, Limonene, Apigenin and some other components show anti-inflammatory effects by cyclooxygenase inhibition, prostaglandin E2 inhibition and other mechanisms. Studies showed 90 % of its essential oil consists of monoterpenes which can be mutually beneficial with extract components.
Conclusion
A. millefolium can play a significant role as a strong antioxidant and anticancer source, positively affecting gastrointestinal inflammations.
In this study, we presented the isolation and characterization of eight novel seco-guaianolide sesquiterpenoids (1-8) and two known guaianolide derivatives (9 and 10), from the aerial part of Achillea alpina L.. Compounds 1-3 were identified as guaianolides bearing an oxygen insertion at the 2, 3 position, while compounds 4-8 belonged to a group of special 3-nor guaianolide sesquiterpenoids. The structural elucidation of 1-8, including their absolute configurations, were accomplished by a combination of spectroscopic data analysis and quantum electronic circular dichroism (ECD) calculations. To evaluate the potential antidiabetic activity of compounds 1-10, we investigated their effects on glucose consumption in palmitic acid (PA)-mediated HepG2-insulin resistance (IR) cells. Among the tested compounds, compound 7 demonstrated the most pronounced ability to reverse IR. Moreover, a mechanistic investigation revealed that compound 7 exerted its antidiabetic effect by reducing the production of the pro-inflammatory cytokine IL-1β, which was achieved through the suppression of the NLRP3 pathway.
Glucose transporter’s mechanism is influenced by the presence of insulin, especially GLUT4 which acts on muscle, adipose, and brain tissue. Medicinal plants with active compounds that were able to regulate the expression and translocation of GLUT helps in the treatment of insulin resistance and hyperglycemia. This study aimed to determine which active compounds isolated from medicinal plants have antihyperglycemic activity on GLUT4 expression in muscle and adipose tissue. The research method used was by searching the literature electronically with the keywords "Plant Isolation", "Chemical Compounds", "Antihyperglycemic Activity", and "Glucose transporter (GLUT) 4". Literature sources in the form of international and national journals have been found on several sites, such as NCBI, Elsevier and Pubmed, and others. A literature search in the form of selected journals from 2016 to 2021. The data were analyzed using the PRISMA (Prefered Reporting Items for Systematic Review and Meta-analyses) method. The results showed that the active substances contained in the plant have antihyperglycemic activity by increasing the translocation and expression of GLUT4 in skeletal muscle cells, adipocytes, and tested-animal models of DM.
Glucose transporter's mechanism is influenced by the presence of insulin, especially GLUT4 which acts on muscle, adipose, and brain tissue. Medicinal plants with active compounds that were able to regulate the expression and translocation of GLUT helps in the treatment of insulin resistance and hyperglycemia. This study aimed to determine which active compounds isolated from medicinal plants have antihyperglycemic activity on GLUT4 expression in muscle and adipose tissue. The research method used was by searching the literature electronically with the keywords "Plant Isolation", "Chemical Compounds", "Antihyperglycemic Activity", and "Glucose transporter (GLUT) 4". Literature sources in the form of international and national journals have been found on several sites, such as NCBI, Elsevier and Pubmed, and others. A literature search in the form of selected journals from 2016 to 2021. The data were analyzed using the PRISMA (Prefered Reporting Items for Systematic Review and Meta-analyses) method. The results showed that the active substances contained in the plant have antihyperglycemic activity by increasing the translocation and expression of GLUT4 in skeletal muscle cells, adipocytes, and tested-animal models of DM.
The variability of the chemical composition of the aerial part of common yarrow (Achillea millefolium L.) was studied as a function of its environmental growth conditions. Samples of four populations of A. millefolium growing wild at various altitudes (1150, 1500, 1700, and 2450 m) above sea level were collected. Their essential oils were obtained by hydrodistillation followed by a determination of their chemical compositions by chromatography–mass-spectrometry. Analytical results showed that the yield of essential oil from the plants depended on the habitat and varied from 0.06 to 0.16 mL/100 g. The composition of the essential oil of A. millefolium comprised 61 constituents, of which 47 were identified, the main group being monoterpenes and their derivatives. The yield of essential oil and its composition were controlled by linear effects of several abiotic factors related to the altitude gradient.
Chemical investigation on the aerial part of Achillea alpina L. led to the isolation of twenty sesquiterpenoids. The structures of the undescribed achigermalides A–H were determined by extensive spectroscopic analysis, including NMR, HRESIMS, UV and IR, and their absolute configurations were established by computational electronic circular dichroism (ECD) method. The X-ray crystal structure for 8α-angeloxy-1β,2β:4β,5β-diepoxy-10β-hydroxy-6βH,7αH,11βH-12,6α-guaianolide was reported for the first time. Glucose consumption was analyzed to investigate the effect of all compounds on palmitic acid (PA)-mediated insulin resistance (IR) in HepG2 cells, and achigermalides D–F, desacetylherbohde A, and 4E,10E-3-(2-methylbutyroyloxy)-germacra-4,10(1)-diene-12,6α-olide appreciably enhanced the glucose consumption at low concentrations of 1.56–6.25 μM. Moreover, achigermalide D decreased the expression of IL-1β and the generation of reactive oxygen species (ROS), and also down-regulated the protein levels of TXNIP, NLRP3, caspase-1 and NF-κB in the Western blot analysis, suggesting achigermalide D mediated IR via the suppression of NLRP3 inflammasome pathway.
This is an overview of plant use for medicinal applications, a practice from old civilizations still used around the world. According to WHO, nearly 80% of people use herbal medicine plant extracts as their primary health solution. Ethnobotany emerges as a research field to document and understand the traditional knowledge about plants and their roles in society. Diseases like diabetes, hypertension, hypercholesterolemia, and cancer are the predominant challenges to global health, chronic diseases accounting for two-thirds of deaths worldwide. This document discusses ethnobotanical studies on many medicinal plants affecting these diseases.
Poor germination and the length of time required for the growth of
seedlings appropriate for planting in the farm affect the cultivation
of medicinal plants such as yarrow (Achillea millefolium L). This
study investigated the abilities of different concentrations of gibberellic acid (GA3) and potassium nitrate (KNO3), mechanical scarification, and hydropriming to improve seed germination and
dormancy release in yarrow. Seeds were germinated on filter
paper in Petri dishes and supplemented with 0, 100, 200, 400, or
800 mg L−1 GA3; 0%, 0.2%, 0.5%, 1.0%, or 2.0% w/v KNO3; 0, 24, or
48 h of hydropriming; and mechanical scarification. Seed priming
with GA3 (800 mg L−1) or 1% KNO3 at 48 h priming time improved
the mean daily germination. Application of 1% KNO3 had the
highest seed germination around 91%. Use of 0.5% KNO3 in 48 h
priming time increased seedling length approximately 52% compared with unprimed seeds. Combinations of scarification and
hydropriming increased germination. The use of priming with
KNO3 at 48 h priming time was effective in improving seed
germination.
Purpose
Herbal medicine has been used for the management of complications of diabetes. The purpose of this paper is to examine the anti-diabetic effects of Achillea millefolium extract on diabetic rats.
Design/methodology/approach
To this aim, 32 male Wistar rats were randomly assigned into four groups in which each group comprised eight rats. The four experimental groups were as follows: control group, diabetic control (DC) group (STZ; 50 mg/kg), diabetic rats, receiving 250 mg/kg hydro-alcoholic extract of the A. millefolium (DAM) and diabetic rats, receiving 5 mg/kg glibenclamide (DG). After 21 days of the treatment course, tissues of the kidney and blood samples were collected for histopathological, biochemical and molecular analysis.
Findings
The concentration of malondialdehyde (MDA) and glucose serum were markedly reduced in the DC group while significantly increased in DG and DAM groups (1.11 ± 0.57 to 19.4 ± 3.5 and 17.8 ± 1.2 p = 0.002 and 325 ± 0.18 to 223 ± 0.11 and 211 ± 0.32 p = 0.02, respectively). Also, the activities of glutathione peroxidase (GPx) and superoxide dismutase (SOD) were markedly reduced in the DC group while significantly increased in DAM and DG groups (9.1 ± 2.21 to 18.7 ± 3.81 and 14.9 ± 3.1 p = 0.03 and p = 0.02, respectively). The concentrations of creatinine, blood urea nitrogen (BUN) and urea were substantially decreased in DAM and DG groups as compared with the DC group (0.49 ± 0.02 to 0.27 ± 0.01 and 0.25 ± 0.01 p = 0.01, 15.6 ± 2.1 to 7.2 ± 0.68 and 8.6 ± 1.2 p = 0.02 and 114 ± 9.4 to 59.8 ± 5.2 and 64 ± 5.2 p = 0.03, respectively). Also, Bcl-2-associated X protein (BAX) expression was significantly decreased in DAM and DG groups as compared with the DC group (1.3 ± 0.32 to 0.91 ± 0.03 and 0.93 ± 0.02 p = <0.01) and Bcl-2 expression were significantly increased in DAM and DG groups as compared with the DC group (0.42 ± 0.05 to 0.88 ± 0.07 and 0.85 ± 0.06 p = 0.01).
Originality/value
Diabetes led to degenerative damages in the kidney of rats and increased the mRNA level of Bax, while treatment with A. millefolium could protect the kidney tissue against diabetes complications and increased the mRNA expression of Bcl-2. This study indicated that A. millefolium extracts not only improves renal function as a result of anti-oxidant activity but also modulates some biochemical factors in diabetic rats.
This study aimed to isolate and characterize the structures of glycoproteins from peas and determine their hypoglycemic activity. The crude pea glycoproteins (PGP) were extracted by hot water and purified by diethylaminoethyl (DEAE)-Sepharose chromatography and Sephadex G-100 size-exclusion chromatography in sequence. Then three main fractions were obtained, namely PGP1, PGP2 and PGP3, with molecular weights of 897 615, 846 740 and 1 194 692 Da, respectively. The physical and chemical properties of the three fractions were evaluated and compared by Fourier transform infrared spectroscopy (FT-IR), nuclear magnetic resonance (NMR), scanning electron microscope (SEM), high performance liquid chromatography (HPLC) and other analytical techniques. The fraction PGP2 with the highest hypoglycemic activity, was screened using the Caco-2 monolayer cell model. It can inhibit the uptake of glucose in the small intestine, as well as the activities of maltase and sucrase. After simulated gastrointestinal digestion, PGP2 significantly enhanced the inhibitory effect of α-glucosidase, and slightly reduced the inhibitory ability of α-amylase. In summary, PGP2 possessed strong hypoglycemic activity after digestion. These results indicated that PGP2 has the potential to be developed into a functional food or natural medicine for the treatment of type 2 diabetes mellitus.
Ethnopharmacological relevance
As a traditional Chinese medicinal, Bidens bipinnata L. has been used to treat many diseases with a long history in China. The anti-diabetic effects of extract from B. bipinnata have been demonstrated in the previous reports.
Aim of the study
The protective effects of flavonoids-rich extract from B. bipinnata (BBTF) on cell damage induced by H2O2 in pancreatic β cell and its potential mechanisms were evaluated.
Materials and methods
MTT, ROS production, nuclear staining and flow cytometry assays were adopted to determine the effects of BBTF on cell viability, production of ROS and cell apoptosis in H2O2-treated INS-1 cell. Cell apoptosis-related proteins expressions were detected by western blot assay.
Results
Pre-treatment of BBTF could significantly increase INS-1 cell viability, inhibit the production of intracellular ROS and reduced the characteristic features of cell apoptosis induced by H2O2 in INS-1 cells. The studies of the underlying mechanism showed that BBTF could regulate Bax and Bcl-2 proteins expressions, suppress the phosphorylation of JNK, ERK and p38, as well as down-regulate Fas and FasL proteins expressions induced by H2O2. The expressions of caspase-8, caspase-9 and caspase-3 were therefore decreased.
Conclusion
The results indicated that flavonoids-rich extract from B. bipinnata could be a natural agent in diabetic prevention and therapy.
Ethnobotanical survey presents the first step in the identification of new bioactive compounds. This study aimed to collect, document and analyse data on the traditional use of medicinal plants in Jablanica district (South-Eastern Serbia) and to compare traditional knowledge with scientifically proven data. Ethnobotanical study was carried out using semi-structured interviews with 103 informants. Discussion of the results was performed after the quantitative ethnobotany factors were calculated. Comparison of the data was done with those of European Medicines Agency (EMA), Yugoslav Pharmacopoeia 1984 (Ph. Jug. IV) and relevant scientific papers. The informants reported data on 89 medicinal plants belonging to 49 families in Jablanica district. The dominantly used families were Lamiaceae and Asteraceae, while Hypericum perforatum L., Mentha × piperita L. and Matricaria chamomilla L. were the species with the highest number of use reports. The most frequently reported indications were respiratory, gastrointestinal, dermatologic, and psychological diseases. The species with most diverse uses were Taraxacum campylodes G.E.Haglund, Achillea millefolium L. and Rosa canina L. According to our results, medicinal plants in Jablanica district are mainly used for treating minor health issues as a mode of primary health care. The wide application of species belonging to Lamiaceae and Asteraceae families can be partially attributed to the fact that many cosmopolitan medicinal plant species belongs to these families and also to their predominance in the flora of Jablanica districts.
Folk or traditional systems of medicines always played an indispensable role in the global healthcare system. Traditional medicine as abundant natural resources has unique advantages in the treatment of diabetes, hyperlipidemia, and other diseases due to its focus on the regulation of body functions as a whole, multi-layered mechanism and approach, which make traditional drugs widely used in all over the world. There is a long history of using plants to treat diabetes in Asia, Africa, and Americas, and some plants and herbal preparations are effective to diabetes mellitus.
Herbal medicines are an integral element of alternative medical care in Mexico, and the best testimony to their efficacy and cultural value is their persistence in contemporary Mexican marketplaces where the highest percentages of medicinal and aromatic plants are sold. This chapter summarizes current trends in research on medicinal plants in Mexico, with emphasis on work carried out at the authors’ laboratories. The most relevant phytochemical and pharmacological profiles of a selected group of plants used widely for treating major national health problems are described.
Type 2 diabetes mellitus (T2DM) is a global pandemic, as evident from the global cartographic picture of diabetes by the International Diabetes Federation (http://www.diabetesatlas.org/). Diabetes mellitus is a chronic, progressive, incompletely understood metabolic condition chiefly characterized by hyperglycemia. Impaired insulin secretion, resistance to tissue actions of insulin, or a combination of both are thought to be the commonest reasons contributing to the pathophysiology of T2DM, a spectrum of disease originally arising from tissue insulin resistance and gradually progressing to a state characterized by complete loss of secretory activity of the beta cells of the pancreas. T2DM is a major contributor to the very large rise in the rate of non-communicable diseases affecting developed as well as developing nations. In this mini review, we endeavor to outline the current management principles, including the spectrum of medications that are currently used for pharmacologic management, for lowering the elevated blood glucose in T2DM.
Aim:
To evaluate the safety and efficacy of human embryonic stem cells (hESCs) for the management of type 2 diabetes mellitus (T2DM).
Methods:
Patients with a previous history of diabetes and its associated complications were enrolled and injected with hESC lines as per the defined protocol. The patients were assessed using Nutech functional score (NFS), a numeric scoring scale to evaluate the patients for 11 diagnostic parameters. Patients were evaluated at baseline and at the end of treatment period 1 (T1). All the parameters were graded on the NFS scale from 1 to 5. Highest possible grade (HPG) of 5 was considered as the grade of best improvement.
Results:
Overall, 94.8% of the patients showed improvement by at least one grade of NFS at the end of T1. For all the 11 parameters evaluated, 54% of patients achieved HPG after treatment. The four essential parameters (improvement in glycated hemoglobin (HbA1c) and insulin level, and fall in number of other oral hypoglycemic drugs with and without insulin) are presented in detail. For HbA1c, 72.6% of patients at the end of T1 met the World Health Organization cut off value, i.e., 6.5% of HbA1c. For insulin level, 65.9% of patients at the end of T1 were able to achieve HPG. After treatment, the improvement was seen in 16.3% of patients who required no more than two medications along with insulin. Similarly, 21.5% of patients were improved as their dosage regimen for using oral drugs was reduced to 1-2 from 5.
Conclusion:
hESC therapy is beneficial in patients with diabetes and helps in reducing their dependence on insulin and other medicines.
Interleukin-1β (IL-1β) has a role in β- cell destruction in autoimmune diabetes by stimulating the expression of inducible nitric oxide synthase (iNOS) that generates the free radical nitric oxide. We aimed to investigate the effect of Achillea millefolium L, as a traditional hypoglycemic agent, on IL-1β and iNOS gene expression of pancreatic tissue in the STZ- induced diabetic rats. Forty adult male Wistar rats were randomly divided into four groups: 1. diabetic control; 2. diabetic rats treated with Achillea millefolium L. extract; 3. normal rats received only extract and 4. negative control (n= 10 each). Diabetes was induced by single i.p. injection of 45 mg/ kg streptozotocin (STZ). Rats in groups 2 and 3 were treated with i.p. injection of Achillea millefolium L. extract (100 mg/ kg/ day) for 14 days. Body weight, serum glucose and insulin levels were assayed at baseline and on days 3, 7, 10 and 14 of the experiment. Finally, the quantity of pancreatic IL-1β and iNOS mRNA was determined by real- time PCR. The mRNA expression level of IL-1β and iNOS genes, was significantly (p<0.001) increased in diabetic rats of group 1. Treatment with Achillea millefolium L. caused a significant (p<0.01) reduction in both IL-1β and iNOS genes expression. Moreover, rats in group 2 had higher insulin level associated with lower glucose level and higher body weight compared to control diabetic group. It seems that beneficial effect of Achillea millefolium L. on STZ- induced diabetes is at least partly due to amelioration of IL-1β and iNOS gene over expression which can have a β-cell protective effect.
Different pharmacological effects of Achillea millefolium including its relaxant effect on smooth muscle have been shown previously. In the present study the stimulatory effect of the plant extract on β-adrenoceptor of tracheal muscle was examined in order to investigate one possible mechanism for its observed relaxant effect. Effect of three concentrations of hydroethanol extract, 10 nM propranolol, and saline on β-adrenoceptor was tested in two experimental groups including; nonincubated tracheal smooth muscles (group 1) and incubated tracheal smooth muscle with chlorpheniramine (group 2). Concentration response curves to isoprenaline were performed in precontracted tracheal smooth muscle in the presence of the extract, propranolol and saline. Values of EC50 and CR-1 were measured. Leftward shifts in isoprenaline curves were observed in the presence of medium and high concentrations of the extract compared with saline in both groups. The values of EC50 obtained in the presence of medium and high concentrations of the extract only in group 1 were nonsignificantly lower than that of saline. The values of CR-1 obtained in the presence of all concentrations of the extract in both groups were negative and significantly different with that of propranolol. The results indicated a small stimulatory effect of the extract on ß2-adrenoceptors.
AimTo evaluate the therapeutic uses of Achillea millifolium in diabetic rats.Methods
Diabetes was induced by single intraperitoneal injection of freshly prepared solution of alloxan monohydrate (150 mg·kg−1 body weight) in Wistar rats of 150-200 g body weight. In this study, the aqueous and methanolic extract of Achillea millifolium was studied for its hypoglycemic and hypolipidemic properties. The rats were divided into several groups, serving as Normal group, Diabetic Control group, Diabetic treated with glibenclamide, and extract treated groups. The blood serum collected from the various groups of rats was analysed for its various biochemical parameters like glucose, cholesterol, triglycerides, VLDL, SGOT, SGPT and ALP. On the 14th day of the experiment the rats were scarified and pancreas was collected for histopathological studies.ResultsThe extracts at dose levels of 250 and 500 mg·kg−1 body weight showed significant (P ≤ 0.05) decrease in blood glucose level, TGL, VLDL, cholesterol, SGOT, SGPT, and ALP in diabetic rats. The extracts prevented the β-cells of pancreas from the cytotoxic effects of Alloxan monohydrate.Conclusion
The results indicate that the extracts as mentioned above are effective in hyperglycemia and can effectively protect against other metabolic aberrations caused by alloxan monohydrate.
Yarrow (Achillea millefolium L.) is an important medicinal plant with different pharmaceutical uses. A. millefolium has been used for centuries to treat various diseases including malaria, hepatitis and jaundice. A. millefolium is commonly prescribed to treat liver disorders. It is also used as an anti-inflammatory agent and is a hepatoprotective herb. A. millefolium is considered safe for supplemental use. It has antihepatotoxic effects also. It is prescribed as an astringent agent. It is prescribed in hemorrhoids, headache, bleeding disorders, bruises, cough, influenza, pneumonia, kidney stones, high blood pressure, menstrual disorders, fever, rheumatoid arthritis, gout, osteoarthritis, hemorrhagic disorders, chicken pox, cystitis, diabetes mellitus, indigestion, dyspepsia, eczema, psoriasis and boils.
Achillea millefolium L. is a member of the Asteraceae family and has been used in folk medicine in many countries. In this study, 19 compounds in A. millefolium essential oil (AM-EO) have been identified; the major components are artemisia ketone (14.92%), camphor (11.64%), linalyl acetate (11.51%) and 1,8-cineole (10.15%). AM-EO can suppress the inflammatory responses of lipopolysaccharides (LPS)-stimulated RAW 264.7 macrophages, including decreased levels of cellular nitric oxide (NO) and superoxide anion production, lipid peroxidation and glutathione (GSH) concentration. This antioxidant activity is not a result of increased superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) activities, but rather occurs as a result of the down-regulation of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and heme oxygenase-1 (HO-1) expression, thus reducing the inflammatory response. Therefore, AM-EO can be utilized in many applications, including the treatment of inflammatory diseases in the future.
As a part of our ongoing effort to identify anti-diabetic constituents from natural sources, we examined the inhibitory activity of the methanol extracts of 12 species of the genus Artemisia, against α-glucosidase and protein tyrosine phosphatase 1B (PTP1B). The methanol extracts of different species exhibited promising α-glucosidase and PTP1B inhibitory activities. Since the methanol extract of Artemisia capillaris exhibited the highest α-glucosidase inhibitory activity together with significant PTP1B inhibitory activity, it was selected for further investigation. Repeated column chromatography based on bioactivity guided fractionation yielded 10 coumarins (esculetin, esculin, scopolin, isoscopolin, daphnetin, umbelliferone, 7-methoxy coumarin, scoparone, scopoletin, 6-methoxy artemicapin C), 8 flavonoids (hyperoside, quercetin, isorhamnetin, cirsilineol, arcapillin, isorhamnetin 3-robinobioside, linarin, isorhamnetin 3-glucoiside), 6 phenolic compounds (1,5-dicaffeoylquinic acid, 3,4-dicaffeoylquinic acid, 3,5-dicaffeoylquinic acid, 3,5-dicaffeoylquinic acid methyl ester, 4,5-dicaffeoylquinic acid, 3-caffeoylquinic acid), and one chromone (capillarisin). Among these compounds, esculetin, scopoletin, quercetin, hyperoside, isorhamnetin, 3,5-dicaffeoylquinic acid methyl ester, 3,4-dicaffeoylquinic acid, and 1,5-dicaffeoylquinic acid exhibited potent α-glucosidase inhibitory activity when compared to the positive control acarbose. In addition, esculetin and 6-methoxy artemicapin C displayed PTP1B inhibitory activity. Interestingly, all isolated dicaffeoylquinic acids showed significant PTP1B inhibitory activity. Therefore, the results of the present study clearly demonstrate the potential of the A. capillaris extract to inhibit α-glucosidase and PTP1B. These inhibitory properties can be largely attributed to a combination of different chemical structures, including coumarins, flavonoids, and dicaffeoylquinic acids, which could be further explored to develop therapeutic or preventive agents for the treatment of diabetes.
This work shows the inhibitory effect on glucosidase and lipase enzymes of 23 medicinal plants described as traditional treatments for diabetes in several Mexican sources. Hydroalcoholic extracts of selected plants were evaluated at 1 mg/mL for glucosidase and 0.25 mg/mL for lipase inhibitory activities, respectively. Camellia sinensis, acarbose, and orlistat were used as positive controls. Dose-response curves were done with the most active species. Sixty percent of all tested extracts inhibited more than 25% of α-glucosidase activity. C. sinensis displayed an inhibition of 85% (IC(50) = 299 μg/mL), while Ludwigia octovalvis and Iostephane heterophylla showed the highest inhibition (82.7 %, IC(50) = 202 μg/mL and 60.6%, CI(50) = 509 μg/mL, resp.). With respect to lipase activity, L. octovalvis and Tecoma stans were the most inhibiting treatments (31.4%, IC(50) = 288 μg/mL; 27.2%, IC(50) = 320 μg/mL), while C. sinensis displayed 45% inhibition (IC(50) = 310 μg/mL). These results indicate that a high proportion of plants used in Mexico as treatment for diabetes displays significant inhibition of these digestive enzymes.
The consensus algorithm for the medical management of type 2 diabetes was published in August 2006 with the expectation that it would be updated, based on the availability of new interventions and new evidence to establish their clinical role. The authors continue to endorse the principles used to develop the algorithm and its major features. We are sensitive to the risks of changing the algorithm cavalierly or too frequently, without compelling new information. An update to the consensus algorithm published in January 2008 specifically addressed safety issues surrounding the thiazolidinediones. In this revision, we focus on the new classes of medications that now have more clinical data and experience.
The purpose of the present study is to investigate the effect of methanolic extracts of Aegles marmelos and Syzygium cumini on a battery of targets glucose transporter (Glut-4), peroxisome proliferator activator receptor gamma (PPARgamma) and phosphatidylinositol 3' kinase (PI3 kinase) involved in glucose transport. A. marmelos and S. cumini are anti-diabetic medicinal plants being used in Indian traditional medicine. Different solvent extracts extracted sequentially were analysed for glucose uptake activity at each step and methanol extracts were found to be significantly active at 100ng/ml dose comparable with insulin and rosiglitazone. Elevation of Glut-4, PPARgamma and PI3 kinase by A. marmelos and S. cumini in association with glucose transport supported the up-regulation of glucose uptake. The inhibitory effect of cycloheximide on A. marmelos- and S. cumini-mediated glucose uptake suggested that new protein synthesis is required for the elevated glucose transport. Current observation concludes that methanolic extracts of A. marmelos and S. cumini activate glucose transport in a PI3 kinase-dependent fashion.
Intestinal glucose absorption comprises two components. One is classical active absorption mediated by the Na+/glucose cotransporter. The other is a diffusive component, formerly attributed to paracellular flow. Recent evidence, however, indicates that the diffusive component is mediated by the transient insertion of glucose transporter type 2 (GLUT2) into the apical membrane. This apical GLUT2 pathway of intestinal sugar absorption is present in species from insect to human, providing a major route at high sugar concentrations. The pathway is regulated by rapid trafficking of GLUT2 to the apical membrane induced by glucose during assimilation of a meal. Apical GLUT2 is therefore a target for multiple short-term and long-term nutrient-sensing mechanisms. These include regulation by a newly recognized pathway of calcium absorption through the nonclassical neuroendocrine l-type channel Cav1.3 operating during digestion, activation of intestinal sweet taste receptors by natural sugars and artificial sweeteners, paracrine and endocrine hormones, especially insulin and GLP-2, and stress. Permanent apical GLUT2, resulting in increased sugar absorption, is a characteristic of experimental diabetes and of insulin-resistant states induced by fructose and fat. The nutritional consequences of apical and basolateral GLUT2 regulation are discussed in the context of Western diet, processed foods containing artificial sweeteners, obesity, and diabetes.
Flavonoids from medicinal plants have been used in traditional medicine to treat a variety of prevalent diseases. Flavones activate the signaling pathways promoting fuel metabolism and insulin sensitizing in hepatocytes and adipocytes, which suggests that flavones may have the potential to exert in vivo antidiabetic and antihyperlipidemic effects. Thus, the aim of the current study was to determine the antidiabetic, antihyperlipidemic and anti-inflammatory effects of tilianin in diabetic rats. Also, to understand the mechanism involved using in vitro 3T3-L1 cells and tissues from experimental animals treated with test samples through molecular profile studies.
Etnopharmacological importance:
Cucurbita ficifolia Bouché (C. ficifolia) is a plant used in Mexican traditional medicine to control type 2 diabetes (T2D). The hypoglycemic effect of the fruit of C. ficifolia has been demonstrated in different experimental models and in T2D patients. It has been proposed that d-chiro-inositol (DCI) is the active compound of the fruit. Additionally, it has been reported that C. ficifolia increases the mRNA expression of insulin and Kir 6.2 (a component of the ATP-sensitive potassium (K(+)ATP) channel, which is activated by sulphonylurea) in RINm5F cells. However, it remains unclear whether C. ficifolia and DCI causes the secretion of insulin by increasing the concentration of intracellular calcium ([Ca(2+)]i) through K(+)ATP channel blockage or from the reservoir in the endoplasmic reticulum (ER).
Material and methods:
The aqueous extract of C. ficifolia was obtained and standardized with regard to its DCI content. RINm5F pancreatic β-cells were incubated with different concentrations (50, 100, 200 and 400μM) of DCI alone or C. ficifolia (9, 18, 36 and 72µg of extract/mL), and the [Ca(2+)]i of the cells was quantified. The cells were preloaded with the Ca(2+) fluorescent dye fluo4-acetoxymethyl ester (AM) and visualized by confocal microscopy. Insulin secretion was measured by an ELISA method. Subsequently, the effect of C. ficifolia on the K(+)ATP channel was evaluated. In this case, the blocker activator diazoxide was used to inhibit the C. ficifolia-induced calcium influx. In addition, the inositol 1,4,5-trisphosphate (IP3)-receptor-selective inhibitor 2-amino-thoxydiphenylborate (2-APB) was used to inhibit the influx of calcium from the ER that was induced by C. ficifolia.
Results:
It was found that DCI alone did not increase [Ca(2+)]i or insulin secretion. In contrast, treatment with C. ficifolia increased [Ca(2+)]i 10-fold compared with the control group. Insulin secretion increased by 46.9%. In the presence of diazoxide, C. ficifolia decreased [Ca(2+)]i by 50%, while insulin secretion increased by 36.4%. In contrast, in the presence of 2-APB, C. ficifolia increased [Ca(2+)]i 18-fold, while insulin secretion remained constant, indicating an additive effect. Therefore, C. ficifolia was not found to block the K(+)ATP channel. However, it did exert an effect by increasing [Ca(2+)]i from the ER, which may partly explain the insulin secretion observed following treatment with C. ficifolia.
Conclusions:
The hypoglycemic properties of C. ficifolia can be explained in part by its effect as a secretagogue for insulin through an increase in [Ca(2+)]i from the calcium reservoir in the ER. Therefore, the mechanism of action of C. ficifolia is different to those of the currently used hypoglycemic drugs, such as sulfonylureas. These results support that C. ficifolia may be a potential natural resource for new agents to control T2D.
We determined the effects of subchronic exposure to aqueous extract of leaves from Achillea millefolium (AE) on enzyme- and non-enzyme-dependent antioxidant systems in rats. Seven days treatment with AE (1 g/kg/twice a day, p.o.) altered the reduced glutathione (GSH) levels and antioxidant enzyme activities in several organs of the animals. Amount of GSH in uterus was increased (73%) while in kidneys it was decreased (23%). Besides, NAD(P)H quinone oxidoreductase 1 (NQO1) activity was increased in forestomach (26%) and in liver (64%), while glutathione S-transferase activity was decreased in the forestomach (32%) and increased in the liver (41%), kidney (35%) and uterus (37%). In preliminary experiments targeting the interaction of AE with acetaminophen (600 mg/kg, p.o.), we observed augmentation of acetaminophen-induced increase of the plasmatic alanine aminotransaminase, aspartate aminotransaminase and lactate dehydrogenase. Overall, the results indicate a potential toxic interaction of AE compounds with xenobiotics that use the glutathione pathway.
Context: There is a need for the discovery of novel natural remedies to prevent and treat metabolic disorders such as hyperglycemia, type II non-insulin-dependent diabetes mellitus and obesity. Several Achillea species have been utilized for centuries all around the world and are generally considered effective as hypoglycemic.
Objective: Considering the ethnobotanical uses of Achillea genus, we evaluated the in vitro inhibitory activity of Achillea tenorii Grande (Asteraceae) extract on α-glucosidase, which is a valuable target to prevent and treat metabolic disorders. We also tested its antioxidant activity. Moreover, the phytochemical profile was discussed from a chemotaxonomic point of view.
Material and methods: In vitro α-glucosidase inhibition of crude ethanolic extract obtained from the aerial parts was assayed as well as the in vitro antioxidant activity (ABTS, DPPH, and FRAP-FZ tests). The extract was characterized by a phytochemical point of view by means of spectroscopic analysis.
Results: The extract results endowed with α-glucosidase inhibitory activity (IC50 32 µg/mL) with a particular mechanism of action definable as un-competitive, which differed from the mechanism observed for the best-known α-glucosidase inhibitor (acarbose and miglitol). In addition, a considerable antioxidant potential has been found for A. tenorii extract, which resulted mainly constituted by phenolic compounds as caffeoylquinic acids, and flavonoids.
Discussion and conclusions: These results suggest the potential of A. tenorii as a possible natural remedy to prevent and treat metabolic disorders of carbohydrates.
α-Glucosidase is a critical associated enzyme with type 2 diabetes mellitus in humans. Inhibition of α-glucosidase is important due to the potential effect of down regulating glucose absorption in patients. In this study, the inhibitory activity of flavone luteolin on α-glucosidase and their interaction mechanism were investigated by multispectroscopic methods along with molecular docking technique. It was found that luteolin reversibly inhibited α-glucosidase in a noncompetitive manner with an IC50 value of (1.72±0.05)×10(-4)molL(-1), and the inhibition followed a multi-phase kinetic process with a first-order reaction. Luteolin had a strong ability to quench the intrinsic fluorescence of α-glucosidase through a static quenching procedure. The positive values of enthalpy and entropy change suggested that the binding of luteolin to α-glucosidase was driven mainly by hydrophobic interactions, and the binding distance was estimated to be 4.56nm. Analysis of synchronous fluorescence, circular dichroism, and Fourier transform infrared spectra demonstrated that the binding of luteolin to α-glucosidase induced rearrangement and conformational changes of the enzyme. Moreover, the results obtained from molecular docking indicated that luteolin had a high affinity close to the active site pocket of α-glucosidase and indirectly inhibited the catalytic activity of the enzyme.
Achillea millefolium L. (Asteraceae), popularly known as "mil-folhas", is well recognized and widely used in Brazilian folk medicine to treat heart and kidney disorders. Among its popularly described effects are diuretic and hypotensive actions.
The diuretic activity of Achillea millefolium L. extracts and its semi-purified fractions, as well as the mechanisms involved, were evaluated in male Wistar rats.
An aqueous extract (AEAM, 125-500mg/kg), hydroethanolic extract (HEAM, 30-300mg/kg), dichloromethane subfractions (DCM-2, 10 and 30mg/kg), or hydrochlorothiazide (10mg/kg), were orally administered and the animals were kept in metabolic cages for 8h for urine collection. To evaluate the involvement of bradykinin and prostaglandins in the diuretic action of A. millefolium, selected groups of rats received HOE-140 (1.5mg/kg, i.p.) or indomethacin (5mg/kg, p.o.), before treatment with a DCM-2 subfraction (30mg/kg). The urinary volume, conductivity, pH, density and electrolyte excretion were measured.
Similar to hydrochlorothiazide, both HEAM and DCM-2, but not AEAM, increased urinary volume and the excretion of Na(+) and K(+) when compared with the control group (vehicle). The diuretic effect of DCM-2 was abolished by HOE-140 (a bradykinin B2 receptor antagonist), as well as by indomethacin (a cyclooxygenase inhibitor).
The present study reveals that extracts obtained from Achillea millefolium are able to effectively increase diuresis when orally administered in rats. This effect depends on both the activation of bradykinin B2 receptors and the activity of cyclooxygenases.
A small series of thiazolidine-2,4-dione and barbituric acid derivatives 1-4 was prepared using a short synthetic route, and all compounds were characterized by elemental analysis, mass spectrometry and NMR ((1) H, (13) C) spectroscopy. Their in vitro relative expression of PPARα and PPARγ was evaluated. Compound 1 showed an increase in the mRNA expression of both PPAR isoforms, as well as the GLUT-4 levels. The antidiabetic activity of compound 1 was determined at 50 mg/Kg single dose using a non insulin dependent diabetes mellitus rat model (NIDDM). The results indicated a significant decrease of plasma glucose levels. Additionally, we performed a molecular docking of compound 1 into the ligand binding pocket of PPARα and PPARγ. In these binding models, compound 1 may bind into the active site of both isoforms showing important short contacts with the PPARγ residues: Tyr 473, His 449, Ser 289, His 323; and PPARα residues: Tyr 464, His 440, Ser 280 and Tyr 314 © 2013 John Wiley & Sons A/S.
The family of transcription factors termed peroxisome proliferator-activated receptors (PPARs) has recently been the focus of much interest for their possible role in the regulation of inflammation and immune responses. PPARalpha and PPARgamma have been implicated in the regulation of macrophage and endothelial cell inflammatory responses. Although PPAR activation has generally been shown to have anti-inflammatory effects, opposite effects have been noted, and results often appear to depend on the ligands being used and the inflammatory parameters being measured. Recently, my laboratory and others have described a role for PPARgamma in the responses of T lymphocytes. Ligands for PPARgamma have been found to inhibit proliferation of activated T cells, and this appears to involve inhibition of IL-2 secretion and/or the induction of apoptosis. However, one problem in the interpretation of many of the studies of PPARgamma, inflammation, and immunity is that ligands thought to be specific for PPARgamma may have regulatory effects on inflammatory parameters that are PPARgamma-independent. Future studies of the role of the PPARs in inflammatory and immune responses should include further studies of T cells, T-cell subsets, and dendritic cells but will have to re-examine the issue of PPAR specificity of the ligands being used. This may require further knockout studies and technology, together with the identification of endogenous and perhaps more specific synthetic PPAR ligands
Achillea millefolium L. (Asteraceae), known as yarrow ("mil folhas"), has been used as folk medicine for gastrointestinal disorders, inflammation, anxiety, and insomnia.
To evaluate the potential anxiolytic-like effect of hydroalcoholic extract of Achillea millefolium L. in animal models.
The present study evaluated the effects of the hydroalcoholic extract from the aerial parts of Achillea millefolium L. in mice subjected to the elevated plus-maze, marble-burying, and open-field tests. Additionally, the GABA(A)/benzodiazepine (BDZ) mediation of the effects of Achillea millefolium was evaluated by pretreatment with the noncompetitive GABA(A) receptor antagonist picrotoxin and the BDZ antagonist flumazenil and by [(3)H]-flunitrazepam binding to the BDZ site on the GABA(A) receptor.
Achillea millefolium exerted anxiolytic-like effects in the elevated plus-maze and marble-burying test after acute and chronic (25 days) administration at doses that did not alter locomotor activity. This behavioral profile was similar to diazepam. The effects of Achillea millefolium in the elevated plus-maze were not altered by picrotoxin pretreatment but were partially blocked by flumazenil. Furthermore, Achillea millefolium did not induce any changes in [(3)H]-flunitrazepam binding.
The results indicate that the orally administered hydroalcoholic extract of Achillea millefolium L. exerted anxiolytic-like effects that likely were not mediated by GABA(A)/BDZ neurotransmission and did not present tolerance after short-term, repeated administration.
Achillinin A (2β,3β-epoxy-1α,4β,10α-trihydroxyguai-11(13)-en-12,6α-olide, 1), a new guaianolide isolated from the flower of Achillea millefolium, exhibited potential antiproliferative activity to A549, RERF-LC-kj and QG-90 cells with 50% inhibitory concentration (IC(50)) values of 5.8, 10 and 0.31 µM, respectively.
Type 2 diabetes mellitus is a multifactorial disease, due to decreased glucose peripheral uptake, and increased hepatic glucose production, due to reduced both insulin secretion and insulin sensitivity. Multiple insulin secretory defects are present, including absence of pulsatility, loss of early phase of insulin secretion after glucose, decreased basal and stimulated plasma insulin concentrations, excess in prohormone secretion, and progressive decrease in insulin secretory capacity with time. beta-cell dysfunction is genetically determined and appears early in the course of the disease. The interplay between insulin secretory defect and insulin resistance is now better understood. In subjects with normal beta-cell function, increase in insulin is compensated by an increase in insulin secretion and plasma glucose levels remain normal. In subjects genetically predisposed to type 2 diabetes, failure of beta-cell to compensate leads to a progressive elevation in plasma glucose levels, then to overt diabetes. When permanent hyperglycaemia is present, progressive severe insulin secretory failure with time ensues, due to glucotoxicity and lipotoxicity, and oxidative stress. A marked reduction in beta-cell mass at post-mortem examination of pancreas of patients with type 2 diabetes has been reported, with an increase in beta-cell apoptosis non-compensated by neogenesis.
We investigated the effects of Achillea millefolium extract in vitro on the growth of primary rat vascular smooth muscle cells (VSMCs) as well as the potential involvement of estrogen receptors (ERs) in this process. In addition, the ability of A. millefolium extract to modulate the NF-κB pathway was tested in human umbilical vein endothelial cells (HUVECs). The fingerprinting of the extract was carried out by HPLC-DAD and LC-MS(n) and main constituents were flavonoids (10%) and dicaffeolylquinic acid derivatives (12%). The extract enhanced VSMC growth at least in part by acting through ERs and impaired NF-κB signaling in HUVECs. The various compounds may act with different mode of actions thus contributing to the final effect of the extract. Our findings support some of the traditional uses of A. millefolium, and suggest potential modes of action as related to its effects on vascular inflammation. Therefore, A. millefolium may induce novel potential actions in the cardiovascular system.
Achillea millefolium L. is a member of the Asteraceae family that is commonly referred to as "yarrow" and has been used in folk medicine against several disturbances including skin inflammations, spasmodic and gastrointestinal disorders, as well as hepato-biliary complaints.
In the present study, we evaluated the efficacy of a hydroalcoholic extract from the Achillea millefolium (HE) for gastroprotective properties and additional mechanism(s) involved in this activity.
Rats were treated with HE and subsequently exposed to both acute gastric lesions induced by ethanol P.A. and chronic gastric ulcers induced by 80% acetic acid. Following treatment, glutathione (GSH) levels and superoxide dismutase (SOD) activity were measured. The activity of myeloperoxidase (MPO) and histological and immunohistochemical analysis were performed in animals with acetic acid-induced gastric ulcers.
Oral administration of HE (30, 100 and 300mg/kg) inhibited ethanol-induced gastric lesions by 35, 56 and 81%, respectively. Oral treatment with HE (1 and 10mg/kg) reduced the chronic gastric ulcers induced by acetic acid by 43 and 65%, respectively, and promoted significant regeneration of the gastric mucosa after ulcer induction denoting increased cell proliferation, which was confirmed by PCNA immunohistochemistry. HE treatment prevented the reduction of GSH levels and SOD activity after acetic acid-induced gastric lesions. In addition, HE (10mg/kg) inhibited the MPO activity in acetic acid-induced gastric ulcers.
The results of the present study indicate that the antioxidant properties of HE may contribute to the gastroprotective activity of this extract.
The aim of the current study was to investigate the oral antidiabetic activity of six structurally related flavonoids: flavone (1), 3-hydroxyflavone (2), 6-hydroxyflavone (3), 7-hydroxyflavone (4), chrysin (5) and quercetin (6). Normoglycemic and STZ-nicotinamide diabetic rats were treated with these flavonoids (50 mg/kg) and the hypoglycemic and antidiabetic effects in acute and sub acute (five days of treatment) experiments were determined. Compounds 1, 5 and 6 were found most active in both experiments in comparison with control group (p<0.05). After five days of administration to STZ-nicotinamide diabetic rats, flavonoids induced a significantly diminishing of total cholesterol, TG and LDL and an augment of HDL compared with the control group (p<0.05). The in vitro inhibitory activity of the compounds against 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) was also evaluated. Quercetin, the most active compound, was docked into the crystal structure of 11beta-HSD1. Docking results indicate potential hydrogen bond interactions with hydroxyl groups of catalytic amino acid residues.
The nuclear receptor PPARs are fundamentally important for energy homeostasis. Through their distinct yet overlapping functions and tissue distribution, the PPARs regulate many aspects of energy metabolism at the transcriptional level. Functional impairment or dysregulation of these receptors leads to a variety of metabolic diseases, while their ligands offer many metabolic benefits. Studies of these receptors have advanced our knowledge of the transcriptional basis of energy metabolism and helped us understand the pathogenic mechanisms of metabolic syndrome.
In suspensions of isolated hepatocytes, two intracellular Ca2+ pools were distinguished in the presence of the metallochrome indicator arsenazo III, first by treatment with the uncoupler carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP) and then with the Ca2+ ionophore A23187. The available evidence indicates that the two pools are of mitochondrial and extramitochondrial origin. Metabolism of t-butyl hydroperoxide by hepatocytes caused release of Ca2+ from both compartments concomitant with oxidation of cellular glutathione and NADPH, which was followed by characteristic alterations in cell surface structure. When NADPH oxidation was prevented by selective inactivation of glutathione reductase, t-butyl hydroperoxide metabolism was without effect on the mitochondrial Ca2+ pool, whereas the loss from the extramitochondrial pool was accelerated. Our results suggest that different regulatory mechanisms modulate mitochondrial (NADPH-dependent) and extramitochondrial (thiol-dependent) Ca2+ compartmentation and that disturbance of normal Ca2+ homeostasis may be critical in peroxide-induced cytotoxicity.
The antihyperglycemic effect of the Antidiabetis herbal preparation ((Myrtilli folium (Vaccinium myrtillus L.), Taraxaci radix (Taraxacum officinale Web.), Cichorii radix (Cichorium intybus L.), Juniperi fructus (Juniperus communis L.), Centaurii herba (Centaurium umbellatum Gilib.), Phaseoli pericarpium (Phaseolus vulgaris), Millefollii herba (Achillea millefolium L.), Morii folium (Morus nigra L.), Valeriane radix (Valleriana officinalis L.), Urticae herba et radix (Urtica dioica L.)), patent No. P-9801091 Zagreb, Croatia was investigated. Two extracts were prepared: ethanol extract (extract 1), and ethanol extract from which ethanol was evaporated on a rotatory evaporator at a temperature of 45 degrees C (extract 2). Extract 1 and extract 2 were administered (in experiment 1) to alloxan-induced non-obese diabetic (NOD) mice in the same dose of 20 mg/kg. Blood glucose was determined before, and 10, 30, 60 and 120 min after the preparation administration. Extract 1 and extract 2 decreased the level of blood glucose by 10 and 20%, respectively, of the initial value (at 0 min, mean = 22.6 +/- 8.3 mmol/l). Serum levels of glucose and fructosamine were determined in NOD mice, NOD mice administered extract 2 in a dose of 20 mg/kg of extract 2, and NOD mice administered acarbose in a dose of 25 mg/100 g chow, in order to verify the hypoglycemic action of extract 2 (in experiment 2). Extract 2 and acarbose were admixed to the chow. The duration of treatment was 7 days. Significantly lower glucose (P < 0.05) and fructosamine (P < 0.001) levels were recorded in extract 2 treated NOD mice as compared with NOD mice. Study results showed extract 2 to significantly decrease the level of glucose and fructosamine in alloxan induced NOD mice. Our future studies will be focused on the search of active principles of the extracts.
The use of herbs is common among diabetics. The aim of this study is to determine the prevalence of the use of herbs among diabetics and which herbs are used. Additionally, to investigate the effect of some demographic characteristics on the use of such herbs.
A cross sectional study was conducted on diabetic patients attending the outpatient clinics in 4 major hospitals in Riyadh, Kingdom of Saudi Arabia. These were: King Khalid University Hospital, King Abdul-Aziz University Hospital, Prince Salman Hospital and Riyadh Medical Complex over a 3-month period which started in September 1999. Patients were interviewed by trained medical students through a predesigned questionnaire that contains items that are related to diabetes and the use of herbs by diabetics.
Two hundred and ninety six diabetic patients out of 300 were interviewed giving a response rate of 98.6%. Fifty-one subjects (17.4%) reported using some form of herbs. The commonest herbs used were myrrh, black seed, helteet, fenugreek and aloes. Approximately 73% of herbs users did not inform their doctor regarding their use of herbs. No statistically significant relationship existed between demographic characteristics and the use of herbs.
The use of herbs is not rare among diabetic patients. Doctors caring for diabetic patients should encourage them to talk regarding the use of herbs as it may effect the outcome and the management of their disease.
The nuclear hormone receptor peroxisome proliferator-activated receptor gamma (PPARgamma) is a member of the PPAR family. The endogenous activators of all members of the PPAR family are a variety of fatty acids, which suggests that the PPARs are highly involved in lipid metabolism. In the present paper, the current understanding of the involvement of PPARgamma in adipocyte proliferation and adipose tissue formation is extensively reviewed, and it is stressed that PPARgamma seems to be a major regulator in the differentiation of adipocytes. Thiazoledinediones (TZDs) are a group of PPARgamma-agonists used in the treatment of type 2 diabetes (T2D) since 1997. They are characterized by their ability to decrease insulin resistance, and have been suggested to slow down the progression of insulin resistance. Treatment with TZD requires several weeks of treatment to decrease plasma glucose levels, but in addition they markedly decrease plasma triglycerides and free fatty acids. A major drawback of treatment with TZD is body fat gain, but some evidence suggests that the fat is redistributed in a favourable direction, that is, from visceral to subcutaneous depots. However, the effect of long-term treatment on weight gain following TZD treatment is unknown, and it may be questioned whether the use of these 'adipogenic compounds' is appropriate, considering that excess body fat is almost a prerequisite for the development of type 2 diabetes.
The crude extract of Achillea millefolium (Am.Cr) was studied for its possible hepatoprotective effect against d-galactosamine (d-GalN) and lipopolysaccharide (LPS) induced hepatitis in mice and antispasmodic effect in isolated gut preparations to rationalize some of the folklore uses. Co-administration of d-GalN (700 mg/kg) and LPS (25 microg/kg) produced 100% mortality in mice. Pre-treatment of animals with Am.Cr (300 mg/kg) reduced the mortality to 40%. Co-administration of d-GalN (700 mg/kg) and LPS (1 microg/kg) significantly raised the plasma alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels compared with values in the control group (p < 0.05). Pre-treatment of mice with Am.Cr (150-600 mg/kg) significantly prevented the toxins induced rise in plasma ALT and AST (p < 0.05). The hepatoprotective effect of Am.Cr was further verified by histopathology of the liver, which showed improved architecture, absence of parenchymal congestion, decreased cellular swelling and apoptotic cells, compared with the toxin group of animals. In isolated rabbit jejunum preparations, Am.Cr caused a concentration-dependent (0.3-10 mg/mL) relaxation of both spontaneous and K(+)-induced contractions as well as shifting the Ca(++) concentration-response curves (CRCs) to the right, similar to that caused by verapamil. These results indicate that the crude extract of Achillea millefolium exhibits a hepatoprotective effect, which may be partly attributed to its observed calcium channel blocking activity.
Achillea millefolium L. (Asteraceae), popularly known as yarrow, has been used in folk medicine to treat complaints such as inflammation, pain, wounds, hemorrhages and gastrointestinal disturbances. The aim of the present study was to assess the safety and efficacy of the aqueous extract (AE) of the plant after chronic exposure. Indeed, the AE was effective in protecting the gastric mucosa against acute gastric lesions induced by ethanol and indomethacin and in healing chronic gastric lesions induced by acetic acid with (ED(50)=32 mg/kg, p.o.). Safety studies were performed in female and male Wistar rats treated daily with AE (0.3-1.2 g/kg, p.o./day) or vehicle (water, 10 ml/kg/day) for 28 or 90 consecutive days. Satellite groups consisted of animals sacrificed 30 days after the end of these treatments. Clinical observations, body and organ weight measurements, gross autopsy, hematology, clinical biochemical and histopathological examinations were performed. Slight changes in liver weight, cholesterol, HDL-cholesterol and glucose were observed in male and female animals. These changes were not correlated with dose or time of exposure of the animals to the AE. Overall, the results show the antiulcer potential of the aerial parts of the Achillea millefolium which is accompanied by no signs of relevant toxicity even at very long chronic exposure.
We have already reported that slowly progressive non-insulin-dependent diabetes mellitus (NIDDM) is produced by a single i.p. injection of a subdiabetogenic dose (100 mg/kg) of streptozotocin (STZ) to 8-week-old male ICR mice. The aim of the present study was to clarify whether or not the progressive NIDDM is induced in ddY, BALB/c, C57BL/6 and ICR mice by the administration of STZ. Eight-week-old male mice of the 4 different strains were administered a single i.p. injection of STZ at various doses (ICR, ddY and BALB/c: 100-200 mg/kg; C57BL/6: 75-150 mg/kg). Among the ddY, BALB/c and C57BL/6 mice, a time course-related rise in non-fasting serum glucose levels throughout the observation period of 1-12 weeks after STZ administration was only induced in the 125 mg/kg STZ ddY and 100 mg/kg STZ ICR mice. In contrast with serum glucose levels, the area of islets and the percentage of the relative number of insulin-immunoreactive cells (beta-cells) to glucagon-immunoreactive cells (alpha-cells) in the 100 mg/kg STZ ICR and 125 mg/kg STZ ddY mice continued to decrease gradually over time. In addition, in low dose STZ mice of both strains, the insulin response to glucose stimulation was extremely impaired over time, although non-fasting serum insulin levels were maintained near normal levels. The rate of the progression of diabetes was faster in the 125 mg STZ ddY mice than in the 100 mg/kg STZ ICR mice.
Isolation and biological characterization of pure compounds was used to identify and characterize estrogenic activity and estrogen receptors (ER) preference in chemical components of Achillea millefolium. This medicinal plant is used in folk medicine as an emmenagogue. In vitro assay, based on recombinant MCF-7 cells, showed estrogenic activity in a crude extract of the aerial parts of A. millefolium. After fractionation of the crude extract with increasing polar solvents, estrogenic activity was found in the methanol/water fraction. Nine compounds were isolated and characterized by HR-MS spectra and 1D- and 2D-NMR techniques. In particular, dihydrodehydrodiconiferyl alcohol 9-O-beta-D-glucopyranoside - a glycosyl-neolignan - was isolated for the first time from the genus Achillea in addition to six flavone derivatives, apigenin, apigenin-7-O-beta-D-glucopyranoside, luteolin, luteolin-7-O-beta-D-glucopyranoside, luteolin-4'-O-beta-D-glucopyranoside, rutin, and two caffeic acid derivatives, 3,5-dicaffeoylquinic acid and chlorogenic acid. Apigenin and luteolin, the most important estrogenic compounds among those tested, were studied for their ability to activate alpha or beta estrogen receptors (ERalpha, ERbeta) using transiently transfected cells. Our results suggest that isolation and biological characterization of estrogenic compounds in traditionally used medicinal plants could be a first step in better assessing further (e.g. in vivo) tests of nutraceutical and pharmacological strategies based on phytoestrogens.
Tournefortia hartwegiana is a Mexican medicinal plant that is used for the treatment of diabetes, diarrhea and kidney pain. In a previous investigation, the methanolic extract of Tournefortia hartwegiana (METh) showed significant hypoglycemic and anti-diabetic properties on normoglycemic and alloxanized rats. In this context, the purpose of the present study was to establish one of the possible modes of action of METh to induce anti-diabetic activity. METh (310mg/kg) effect on alpha-glucosidase activity was investigated. METh intragastric administration was conducted to determine oral glucose tolerance test (OGTT), using different substrates: glucose, sucrose and maltose. The increase in plasma glucose level was significantly suppressed (P<0.05) by the extract after substrates administration. On the other hand, METh inhibited alpha-glucosidase activity in vitro, in a concentration-dependent manner (IC(50) of 3.16mg/mL). These results suggest that METh might exert its anti-diabetic effect by suppressing carbohydrate absorption from intestine, and thereby reducing the post-prandial increase of blood glucose. On the other hand, the bio-guided fractionation of this extract led to the isolation of: beta-sitosterol (1), stigmasterol (2), lupeol (3), ursolic acid (4), oleanolic acid (5), saccharose (6) and myo-inositol (7), using various chromatographic techniques.
The in vitro antimicrobial and antioxidant activities of the essential oil and methanol extracts of Achillea millefolium subsp. millefolium Afan. (Asteraceae) were investigated. GC-MS analysis of the essential oil resulted in the identification of 36 compounds constituting 90.8% of the total oil. Eucalyptol, camphor, alpha-terpineol, beta-pinene, and borneol were the principal components comprising 60.7% of the oil. The oil strongly reduced the diphenylpicrylhydrazyl radical (IC(50)=1.56 micro g/ml) and exhibited hydroxyl radical scavenging effect in the Fe(3+)-EDTA-H(2)O(2) deoxyribose system (IC(50)=2.7 micro g/ml). It also inhibited the nonenzymatic lipid peroxidation of rat liver homogenate (IC(50)=13.5 micro g/ml). The polar phase of the extract showed antioxidant activity. The oil showed antimicrobial activity against Streptococcus pneumoniae, Clostridium perfringens, Candida albicans, Mycobacterium smegmatis, Acinetobacter lwoffii and Candida krusei while water-insoluble parts of the methanolic extracts exhibited slight or no activity. This study confirms that the essential oil of Achillea millefolium possesses antioxidant and antimicrobial properties in vitro.
Oxidative stress is produced under diabetic condition and is likely involved in progression of pancreatic damage found in diabetes. In the present study, we examined possible protective effect of Achillea santolina L. (Compositae) against pancreatic damage in streptozotocin (STZ)-treated diabetic rats. Achillea santolina extract (ASE) is used by the traditional healers in many part of Iraq, as a hypoglycaemic agent. We evaluated the effect of ASE on blood glucose level, serum nitric oxide (NO) concentration and the oxidative stress status in rat pancreatic tissue. STZ was injected intraperitonealy at a single dose of 40mgkg(-1) to induce diabetes. ASE (0.1g/kgday) was orally administered to a group of diabetic rats for 30 consecutive days. Results showed significant reduction in the activities of superoxide dismutase (SOD), catalase (CAT) and pancreatic glutathione (GSH) levels in the diabetic rats compared to the control subjects. On the other hand, blood glucose level, serum NO, malondialdehyde (MDA), a marker of lipid peroxidation, protein oxidation indices including protein carbonyl (PCO) and advanced oxidation protein products (AOPP) were significantly elevated in pancreas of the diabetic group. Treatment with ASE reduced blood glucose level, serum NO, pancreatic MDA, PCO and AOPP. In addition, the content of GSH was restored to the normal level of the control group. Furthermore, ASE significantly increased CAT and SOD activities in ASE-treated rats. Based on our data, it can be concluded that Achillea santolina have a high hypoglycaemic activity and this may be attributed to its antioxidative potential.
Achillea millefolium L. s.l. is a cytogenetically, morphologically, and chemically polymorphic aggregate. Besides the sesquiterpenes that possess chemotaxonomic relevance and mediate the antiphlogistic activity, the plant contains phenolic compounds such as dicaffeoylquinic acids and flavonoids causing choleretic and spasmolytic effects. To evaluate their contribution to the chemotaxonomy of European taxa of the A. millefolium group, we developed a SPE-HPLC/UV method that allows quantification of the phenolic constituents in the different taxa. The investigated species displayed differences in the quantitative and qualitative composition of phenolic acids and flavonoids. Hence, they seem to be of chemotaxonomic significance, especially for the distinction of the diploid taxa. Combining the obtained results with the data of the sesquiterpene analyses gives a comprehensive insight into the distribution of those pharmacologically relevant plant constituents in the A. millefolium group.
In this document, we have integrated knowledge about two major cellular markers found in cells of the adipocyte lineage (an adipogenic marker and a metabolic marker). This review provides information as to how differentiation of a cell (such as an adipofibroblast, fibroblast or preadipocyte) to become a viable (and new) adipocyte is under different regulation than that experienced by an immature adipocyte that is just beginning to accumulate lipid. The differentiation, prior to lipid-filling, involves PPARgamma. Subsequently, lipid-filling of the adipocyte relies on a late subset of genes and, depending on depot specificity, involves GLUT-4 or any number of other metabolic markers.
Achillea millefolium L. s.l. is traditionally used not only in the treatment of gastro-intestinal and hepato-biliary disorders, but also as an antiphlogistic drug. As various proteases, for instance human neutrophil elastase (HNE) and matrix metalloproteinases (MMP-2 and -9), are associated with the inflammatory process, the aim of this study was to test a crude plant extract in in vitro-protease inhibition assays for understanding the mechanisms of anti-inflammatory action. Furthermore, two fractions enriched in flavonoids and dicaffeoylquinic acids (DCQAs), respectively, were also tested in order to evaluate their contribution to the antiphlogistic activity of the plant. The extract and the flavonoid fraction inhibited HNE showing IC(50) values of approximately 20 microg/ml, whereas the DCQA fraction was less active (IC(50)=72 microg/ml). The inhibitory activity on MMP-2 and -9 was observed at IC(50) values from 600 to 800 microg/ml, whereas the DCQA fraction showed stronger effects than the flavonoid fraction and the extract. In conclusion, the in vitro-antiphlogistic activity of Achillea is at least partly mediated by inhibition of HNE and MMP-2 and -9. After the recently described spasmolytic and choleretic effects the obtained results give further insights into the pharmacological activity of Achillea and confirm the traditional application as antiphlogistic drug.
The present investigation was designed to determine the in vivo antidiabetic effect of naringenin (NG) in normoglycaemic and diabetic rat models through blood glucose (GLU) measurements following acute and subchronic time periods. Possible modes of action of NG were investigated and its acute toxicity determined.
Normoglycaemic and non-insulin-dependent diabetes mellitus (NIDDM) rat models were treated for acute and subchronic (5 days) time periods with 50 mg/kg/day of NG. Blood biochemical profiles were determined after 5 days of the treatment in normoglycaemic and NIDDM rats using commercial kits for GLU, triglycerides (TG), total cholesterol (CHOL) and high-density lipoprotein (HDL). In order to elucidate its antidiabetic mode of action, NG was administered intragastrically and an oral glucose tolerance test performed using GLU and sucrose (2 g/kg) as substrates. The inhibitory effect of a single concentration of NG (10 microM) on 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) activity in vitro was determined. Finally, the preclinical safety and tolerability of NG was determined by toxicological evaluation in mice and rats using Organization for Economic Cooperation and Development (OECD) protocols.
Intragastrically administered NG (50 mg/kg) induced a significant decrease in plasma GLU in normoglycaemic and NIDDM rat models (p < 0.05) following acute and subchronic time periods. After 5 days of administration, NG produced significant diminished blood GLU and TG levels in streptozotocin-nicotinamide-induced diabetic rats. The administration of NG to normal rats significantly increased the levels of TG, CHOL and HDL (p < 0.05). NG (5 and 50 mg/kg) induced a total suppression in the increase of plasma GLU levels after administration of substrates (p < 0.01), but NG did not produce inhibition of alpha-glucosidase activity in vitro. However, NG (10 microM) was shown to inhibit 11beta-HSD1 activity by 39.49% in a cellular enzyme assay. Finally, NG showed a Medium Lethal Dose LD(50) > 5000 mg/kg and ranking at level five based on OECD protocols.
Our findings suggest that NG may exert its antidiabetic effect by extra-pancreatic action and by suppressing carbohydrate absorption from intestine, thereby reducing the postprandial increase in blood GLU levels.
Antidiabetics effect of Achillea santolina aqueous leaves extract
- Al-Awwadi
Al-Awwadi, N.A.J., 2013. Antidiabetics effect of Achillea santolina aqueous leaves extract.
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Journal of Ethnopharmacology 212 (2018) 1-7
Mecanismos moleculares queue intervienen en la regulación de la síntesis de insulina por glucosa
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118-120 (In Spanish).