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Cyclooxygenase-2 inhibitory withanolides from Withania somnifera leaves
Abstract
Four novel withanolide glycosides and a withanolide have been isolated from the leaves of Withania somnifera. The structures of the novel compounds were elucidated as physagulin D (1→6)-β-d-glucopyranosyl-(1→4)-β-d-glucopyranoside (1), 27-O-β-d-glucopyranosyl physagulin D (2), 27-O-β-d-glucopyranosyl viscosalactone B (3), 4,16-dihydroxy-5β, 6β-epoxyphysagulin D (4), and 4-(1-hydroxy-2,2-dimethylcyclo-propanone)-2,3-dihydrowithaferin A (5) on the basis of 1D-, 2D NMR and MS spectral data. In addition, seven known withanolides withaferin A (6), 2,3-dihydrowithaferin A (7), viscosalactone B (8), 27-desoxy-24,25-dihydrowithaferin A (9), sitoindoside IX (10), physagulin D (11), and withanoside IV (12) were isolated. These withanolides were assayed to determine their ability to inhibit cycloxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) enzymes and lipid peroxidation. The withanolides tested, except compound 9, showed selective COX-2 enzyme inhibition ranging from 9 to 40% at 100μg/ml. Compounds 4, 10 and 11 also inhibited lipid peroxidation by 40, 44 and 55%, respectively. The inhibition of COX-2 enzyme by withanolides is reported here for the first time.
... Two withanolides with unmodified skeletons containing a free ketone at C-12 were reported from various plants, namely (-)-jaboromagellonine (38) from Jaborosa magellanica [49] and jaborosalactone 44 (39) from J. kurtzii [50]. A 12-oxygenated withanolide, daturalactone 7 (40), was isolated from Datura ferox collected in Argentina [51]. An intriguing example includes a C29 withanolide from the bark of Eucalyptus globulus (41) with an ethyl substituent at C-25 instead of the usual methyl group [52]. ...
... From the aerial parts of Premna fulva, a plant used in Zhuang medicine, a unique metabolite, premnafulvol A (607), was isolated. This compound features a distinct 6/5/7/3-fused tetracyclic 40 carbon skeleton [483]. Spiroseoflosterol (608), an unusual ergostane steroid, was isolated from Butyriboletus roseoflavus and demonstrated cytotoxicity against liver cancer cell lines [484]. ...
This article presents a comprehensive overview of recent discoveries and advancements in the field of steroid chemistry, highlighting the isolation and characterization of various steroidal compounds from natural sources. The paper discusses a wide range of steroids, including pregnane steroids, steroidal alkaloids, ketosteroids, and novel triterpenoids, derived from marine organisms, fungi, and plants. Significant findings include the isolation of bioactive compounds such as the cytotoxic erectsterates from microorganisms, soft corals, the unusual tetracyclic steroid penicillitone from a fungal culture, and innovative steroidal derivatives with potential anti-inflammatory and anticancer activities. The synthesis of steroids from microorganisms as a tool for pharmaceutical development is also explored, showcasing the role of microbial biotransformation in generating steroidal drugs. Additionally, the paper emphasizes the ecological and medicinal relevance of these compounds, which are often used in traditional medicine and have potential therapeutic applications in treating diseases like cancer and microbial infections. This article serves as a vital resource for researchers interested in the chemical diversity of steroids and their applications in drug discovery and development.
... Furthermore, numerous in vitro and in vivo tests were done on different parts of W. somnifera. e leaves of W. somnifera showed anti-inflammatory activity against stainless steel implant-induced inflammation in adult zebra fish [25]; anxiolytic and antineuroinflammatory activity against systemic lipopolysaccharide-induced neuroinflammation in albino rats and in in vitro test [26,27]; antimalarial activity in Plasmodium berghei infected mice [28]; antidiabetic and antihyperlipidemic activity in alloxan-induced diabetic rats [29,30]; cyclooxygenase-2 (COX-2) enzyme inhibition [31]; and antigenotoxicity, antioxidant, and anticancer effects against hepatocellular carcinoma cell line [32]. e qualitative phytochemical screening test also revealed the existence of tannins, cardiac glycosides, steroids, reducing sugars, flavonoids, saponins, phenols, and alkaloids [33,34]. ...
... Tannins also showed blocking of fluid secretion as a result of denaturing of proteins and by forming a tannate complex coat over the surface of the intestinal mucus which makes the intestinal mucus more resistant to chemical alteration and reduces secretion [61]. Withanolides, extracted from the leaves of W. somnifera, revealed COX-2 enzyme, which converts arachidonic acid into prostaglandin, an inhibition that contributed to the antidiarrheal activity of the plant [31]. Prostaglandin induces diarrhea as a result of overstimulation of secretion and inhibition of fluid absorption in the lumen of the gastrointestinal tract. ...
Background:
Withaniasomnifera is an important medicinal plant for the treatment of diarrhea in Ethiopian folklore medicine. The aim of this study was to evaluate the antidiarrheal activity of Withania somnifera leaves in Swiss albino mice.
Materials and methods:
Hydromethanolic crude extraction and solvent fractionation were done using cold maceration technique. 80% methanol was used as a solvent in crude extraction, while distilled water, n-butanol, and chloroform were employed during fractionation. Castor oil-induced diarrhea, enteropooling, and gastrointestinal motility models were employed to evaluate antidiarrheal activity. Mice were randomly divided into five groups (six mice per group): negative control, which received 2% Tween 80 in distilled water; positive control, which received 3 mg/kg loperamide; and three test groups (III, IV, and V), which were treated with 100 mg/kg, 200 mg/kg, and 400 mg/kg of crude extract and solvent fractions, respectively.
Results:
The crude extract, aqueous, and n-butanol fractions significantly delayed the onset of diarrhea at 200 mg/kg and 400 mg/kg dose. There was a significant reduction in the number and weight of stools at all tested doses of the crude extract and aqueous fraction, and at 200 mg/kg and 400 mg/kg of n-butanol fraction. Significant reduction in volume and weight of intestinal contents was observed at all tested doses of the crude extract, and at 200 mg/kg and 400 mg/kg of aqueous and n-butanol fractions. All tested doses of the crude extract and 200 mg/kg and 400 mg/kg of the aqueous and n-butanol fractions significantly reduced the motility of charcoal meal.
Conclusion:
This study demonstrated that the crude extract and solvent fractions of the Withania somnifera leaves have antidiarrheal activity and supported the folklore use of the plant.
... A chlorinated steroidal lactone, 27-acetoxy-4β,6α-dihydroxy-5β-chloro-1-383 oxowitha-2,24-dienolide (46), a diepoxy withanolide, 5β,6β,14α,15α-diepoxy-384 4β,27-dihydroxy-1-oxowitha-2,24-dienolide (47) The cylooxigenase-2(COX-2) inhibition potential of the withanolides isolated from 494 W. somnifera has been reported by Jayaprakasam and Nair (2003) and Chen et al. 495 (2011 The antifungal activity of W. adpressa has been reported for the leaf of this plant, but 521 other parts have to be investigated. No chemical constituents have been identified 522 which are responsible for this antifungal activity. ...
... 4)-β-D-glucopyranoside (63), 27-O-β-D-glucopyranosyl 422 viscosalactone B (64), physagulin D (65), withaferin A, 2,3-dihydrowithaferin A 423(66), 4-(1-hydroxy-2,2-dimethylcyclo-propanone)-2,3-dihydrowithaferin A (67), 424 24, and withanoside IV (51). These compounds selectively inhibited COX-2 enzyme 425 by up to 40% and lipid peroxidation up to 55% at 100 μg/mL concentrations 426(Jayaprakasam and Nair 2003 ...
Plants belonging to Withania genus are well-known medicinal plants and are commonly used as herbal medicine in the Ayurvedic health system. These plants belong to the family Solanaceae and comprise of 23 known species distributed in North Africa, the Middle East, Asia, the Mediterranean, and the Canary Islands. However, only six species, namely, Withania somnifera (L.) Dunal, Withania coagulans (Stocks) Dunal, Withania adpressa Coss, Withania aristata (Aiton) Pauquy, Withania frutescens (L.) Pauquy, and Withania obtusifolia Täckh, are extensively investigated with regard to their pharmacological properties and bioactive constituents. Therefore, in this chapter, the traditional uses of the six Withania species and the pharmacological validations of the plants and plant-derived constituents are discussed. Applications of the bioactive constituents in drug discovery are explained by discussing the semisynthetic modifications and structure-activity relationships.
... 24, and withanoside IV (51). These compounds selectively inhibited COX-2 enzyme by up to 40% and lipid peroxidation up to 55% at 100 μg/mL concentrations (Jayaprakasam and Nair 2003). A few withanolides isolated from the methanolic extract of the whole plant material inhibited cholinesterase enzyme. ...
... The cylooxigenase-2(COX-2) inhibition potential of the withanolides isolated from W. somnifera has been reported by Jayaprakasam and Nair (2003) and Chen et al. (2011). The only inactive compound contained the saturated lactone group in ring E (79). ...
The purpose of this review is to introduce the readers about the pharmacological and chemical aspects of the genus Withania. Present review has a brief description about almost all the pharmacological and chemical studies made on the six different species of this genus and tells about the future prospectus of these plants in the field of drug discovery and health care. It also provides key information about the structure activity relationship in withanolides which are the major bioactive constituents of these plants.
... In another outline, curcumin was found to decrease levels of salivary cortisol, TNFα, IL-1β, and increase plasma Brain Picked Neurotropic part (BDNF), in pack treated with curcumin 41 . Lopresti et al. 42 found huge expansions in the urinary atomic markers leptin, standard plasma endothelin-1, substance P, and thromboxane B2, which are all ordinarily connected with the development structure for the curcumin impetus. In an exact framework, Costa et al. 43 idea that Curcuma longa supplementation changed lead and caused neurotoxic aftereffects in Alzheimer's sickness. ...
Numerous neuropsychiatric and neurodegenerative problems, such as anxiety, cerebrovascular problems, depression, seizures, Parkinson’s disease, and others. are currently dominating the scene as a result of their high-stress lifestyle. Treatment of these issues with postponed association of produced drugs will provoke serious coincidental impacts. In recent years, researchers have stood out sufficiently to be noticed in their investigation of phytochemicals as potential treatments for neurological issues. The unique phytochemicals found in various plants, such as alkaloids, steroids, terpenoids, saponins, phenolics, and flavonoids, contribute to the neuroprotective effects of nootropic flavors. Phytocompounds from restorative plants have a significant impact on maintaining the mind’s compound equilibrium by following up on the capability of receptors for the major inhibitory synapses. recovering plants, for example, Valeriana officinalis, Nardostachys jatamansi, Withania somnifera, Bacopa monniera, Ginkgo biloba and Panax ginseng have been utilized broadly in various standard frameworks of treatment considering their adaptogenic, psychotropic and neuroprotective properties. The significance of phytochemicals’ system of action and beneficial potential in relation to neuroprotective capacity and other issues is the subject of this study.
... Cyclooxygenase-2 (COX-2) inhibitor screening kit (Thermofisher, Scientifics, India) measured fluorescence during prostaglandin G2 production by COX-2 enzyme. prostaglandin G2 produced was assessed for the anti-inflammatory activity of W. somnifera extract and composition [16]. ...
The medicinal plant Withania somnifera, usually referred to as Ashwagandha, is a member of the Solanaceae family. The presence of Withanolides in the roots is responsible for a number of pharmacological effects in Ashwagandha. Withanolides have been demonstrated to be an effective neuronal, immune, anti-stress, and anti-cancer agent. However, Withanolides demonstrated limited permeability, lowering the bioavailability and efficacy of active compounds. The goal of the study was to ascertain the biological efficacy of Ashwagandha Composition, a blend of W. somnifera milk extract and water extract (1:1) with a high concentration of Withanolides (3-5%), at lower dosages with improved bioabsorption compared to pure Ashwagandha Hydro ethanolic extracts fortified with 2.5% withanolides. The W. somnifera Composition was assessed for its bioabsorption and bioefficacy by exploring its intestinal absorption capacity, Acetylcholinesterase Inhibition (82%), antioxidant potential (91%), glutathione reduction potential (15.6%), anti-inflammatory activity (87.2%), and anti-cancer activity. Additionally, Ashwagandha Composition was also evaluated for its safety profile. We found W. somnifera Composition (1:1) is more bioavailable and showed higher biological activity than the Ashwagandha Hydro ethanolic extract fortified with 2.5% withanolides (Ashwagandha extract). Hence, the W. somnifera a Composition can be used as a therapeutic medication once its safety concerns are addressed by in vivo trials.
... In the current study, the apparent decrease in COX2 immunoreactivity in ASH/MTX group, is supported by Jayaprakasam and Nair (27) and Ichikawa et al (28) who reported that Ashwagandha has an antiinflammatory effect with a selective COX2 enzyme inhibitory effect. It has been suggested that the anti-inflammatory effect of Ashwagandha is attributed to its bioactive components withanolides specifically withaferin A, which has the ability to inhibit the activation of Nuclear Factor Kappa B (NF-κB), and alpha-2 macroglobulin (29) . ...
Introduction: Oral mucositis is a common side effect of methotrexate chemotherapy; it
represents a challenge for a successful cancer treatment, as it may lead to discontinuity of the chemotherapy. Ashwagandha is one of the most familiar Ayurveda herbs in India. Recently, it has gained attention due to its favorable biological effects.
Aim: Investigation of the possible protective effect of Ashwagandha roots extract on
methotrexate-induced oral mucositis in albino rats.
Materials and methods: 40 rats were divided equally into 4 groups: (C): received distilled water, (ASH): received 300mg/kg ashwagandha root extract for 8 days, (MTX): received single dose of 60 mg/kg intraperitoneal injection of methotrexate on day 4, and (MTX/ASH): received 300mg/kg ashwagandha root extract daily for 8 days interrupted with 60 mg/kg i.p injection of methotrexate on day 4.
Results: Histopathological examination revealed normal appearance of tongue and buccal mucosa in C and ASH groups. In MTX group there was atrophy of tongue papilla, decrease of epithelial thickness, flattening of rete pegs, nuclear pyknosis, nuclear hyperchromatism, karyorrhexis, disruption of basement membrane, inflammatory cells infiltrate, blood vessels congestion, muscle atrophy in both mucosae. In MTX/ASH group, both mucosae maintained normal appearance. Immunohistochemical results revealed significant decrease of Ki67 staining in MTX group compared to C and MTX/ASH groups in both mucosae, COX2 staining revealed significant increase in MTX group compared to C and MTX/ASH groups.
Conclusion: Prophylactic administration of Ashwagandha root extract ameliorated the oral mucositis induced by methotrexate chemotherapy, therefore it could be a good adjuvant therapy during chemotherapeutic treatment.
... It is renowned for its numerous medicinal properties including antioxidative, anti-inflammatory, antidiabetic, antistress, hepatoprotective, immunomodulatory, anticonvulsant, and hypocholesterolemic activities (Bhattacharya et al. 2000;Pandey et al. 2014). These therapeutic properties are attributed to withanolides and their glycosylated derivatives, known as withanosides or glycowithanolides, found in roots (Matsuda et al. 2001;Zhao et al. 2002) and leaves (Jayaprakasam and Nair 2003). Withanosides, characterized by glucose units attached to C-3 or C-27 positions of withanolides, are suggested to play a crucial role in the plant's defence against biotic and abiotic stresses (Chaturvedi et al. 2011;Misra et al. 2016). ...
The medicinal properties of Ashwagandha ( Withania somnifera L. Dunal) are attributed to the presence of unique class of natural products called as withanolides and their glycosylated forms, withanosides. Withanosides are proposed to be formed from withanolides by the action of glycosyltransferases (GTs). This study reports the functional characterization of two GTs ( WsGT4 and WsGT6 ) from W. somnifera that exhibited induced expression in response to methyl jasmonate treatment and showed highest expression in leaves compared to other tissues. Biochemical assays with recombinant WsGT proteins showed that WsGT4 and WsGT6 formed glycosylated products with four and one of the seven tested withanolides substrates, respectively. WsGT4 catalyzed product formation using withanolide A, withanolide B, withanone, and 12-deoxywithastramonolide as substrates, with UDP-glucose serving as the glucose donor, while WsGT6 catalyzed the product formation only with withaferin A as substrate employing either UDP-glucose or UDP-galactose as sugar donors. Moreover, in planta studies through virus-induced gene silencing and transient overexpression of WsGT4 and WsGT6 in W. somnifera leaves modulated the levels of withanolides and withanosides, indicating their role in withanosides biosynthesis. Furthermore, while individual silencing of both WsGT4 and WsGT6 in W. somnifera reduced the tolerance to Pseudomonas syringae DC3000 growth, their overexpression enhanced the tolerance to the bacterium in W. somnifera . Taken together, these results shed light on the roles of WsGT4 and WsGT6 in withanoside biosynthesis and defence against model bacterial pathogen in W. somnifera .
... In ring B, the 1α,3β-dihydroxy arrangement with a 5,6-double bond is reported from the 3β-O-glycosides isolated from WS and includes compounds 26 to 29. 35,40 This group also includes three withanolides with an additional sugar moiety at C-27, withanosides VIII (30), IX (31), and X (32) and an analog of withanoside VI (28) with a monosaccharide at C-3 called withanoside XI (33). 45,46 Coagulin Q (34) has the same aglycone as withanoside VI, but at C-3, there is a monosaccharide unit. All carbohydrate units attached are always β-D-glucose. ...
Ashwagandha, also known as Withania somnifera (WS), is an ayurvedic botanical plant with numerous applications in dietary supplements and traditional medicines worldwide. Due to the restorative qualities of its roots, WS has potent therapeutic value in traditional Indian (Ayurvedic, Unani, Siddha) and modern medicine recognized as the “Indian ginseng”. The presence of phytochemical bioactive compounds such as withanolides, withanosides, alkaloids, flavonoids, and phenolic compounds has an important role in the therapeutic and nutritional properties of WS. Thus, the choice of WS plant part and extraction solvents, with conventional and modern techniques, plays a role in establishing WS as a potential nutraceutical product. WS has recently made its way into food supplements and products, such as baked goods, juices, beverages, sweets, and dairy items. The review aims to cover the key perspectives about WS in terms of plant description, phytochemistry, structural significance, and earlier reported extraction methodologies along with the analytical and pharmacological landscape in the area. It also attempts to iterate the key limitations and further insights into extraction techniques and bioactive standardization with the regulatory framework. It presents a key to the future development of prospective applications in foods such as food supplements or functional foods.
... The plant genus Withania has a long history of medicinal use, including the treatment of conditions, such as conjunctivitis, inflammation, stress, bronchitis, anxiety, neurological illnesses, ulcers, and liver disease [15]. The genus Withania possesses multiple pharmacological roles including anticholinesterase, analgesics, cures, immunomodulators, and antioxidants [16][17][18][19][20][21][22][23]. Withania adpressa Coss. ...
Withania adpressa Coss. ex is a plant used in traditional medications. Antioxidant, antibacterial, and antifungal properties of the essential oil from leaves of Withania adpressa Coss ex. (EOW) were investigated. EOW was extracted using a Clevenger apparatus, and its volatile compounds were characterized by GC-MS. Antioxidant potency was determined using DPPH, FRAP, and TAC assays. Antibacterial effects were determined vs. Escherichia coli, Klebsiella pneumonia, Staphylococcus aureus, and Streptococcus pneumonia; while its antifungal efficacy was determined vs. Candida albicans, Aspergillus flavus, Aspergillus niger, and Fusarium oxysporum using the disc diffusion and minimum inhibitory concentration bioassays. A chromatographic analysis showed that EOW contained eight phytochemical compounds constituting 99.14% of the total mass of oil. Caryophyllene (24.74%), Longifolene (21.37%), δ-Cadinene (19.08%), and Carene (14.86%) were predominant compounds in EOW. The concentrations required to inhibit 50% of free radical (IC50) values of antioxidant activities of EOW were 0.031 ± 0.006 mg/mL (DPPH), 0.011 ± 0.003 mg/mL (FRAP), and 846.25 ± 1.07 mg AAE/g (TAC). Inhibition zone diameters of EOW vs. bacteria were 18.11 ± 0.5 mm (E. coli), 17.10 ± 0.42 mm (S. aureus), 12.13 ± 0.31 mm (K. pneumoniae), and 11.09 ± 0.47 mm (S. pneumoniae), while MIC values were 51 ± 3, 47 ± 5, 46 ± 3 and 31 ± 1 µg/mL, respectively. Inhibition zone diameters of EOW vs. fungi were 31.32 ± 1.32, 29.00 ± 1.5, 27.63 ± 2.10, and 24.51 ± s1.07 mm for A. flavus, C. albicans, F. oxysporum, and A. niger, respectively. MIC values were 8.41 ± 0.40, 28.04 ± 0.26, 9.05 ± 0.76, and 22.26 ± 0.55 µg/mL, respectively. Importantly, the highest dose of EOW (1 mg/mL) showed negligible (~5%) cytotoxicity against MCF-12, a normal human epithelial cell line derived from the mammary gland, thus underscoring its wide safety and selectivity against tested microbes. To sum it up, EOW has exhibited promising antioxidant and antimicrobial properties, which suggests potential to abrogate antibiotic resistance.
... This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). mation, etc. (Archana and Namasivayam, 1998;Jayaprakasam and Nair, 2003;Bhattacharya and Muruganandam, 2003) as well as model organisms that exhibit immunomodulatory properties (Sharma et al., 2010). There are 61 species in the Withania genus that have been identified worldwide, however, only five were accepted as names: Withania somnifera (L.) Dunal, Withania japonica (Franch and Sav), Withania coagulans (Stocks) Dunal, Withania begonifolia (Roxb.) ...
Genomic studies not only help researcher not only to identify genomic features in organisms, but also facilitate understanding of evolutionary relationships. Species in the Withania genus have medicinal benefits, and one of them is Withania frutescens, which is used to treat various diseases. This report investigates the nucleotides and genic features of chloroplast genome of Withania frutescens and trying to clarify the evolutionary relationship with Withania sp and family Solanaceae. We found that the total size of Withania frutescens chloroplast genome was 153.771 kb (the smallest chloroplast genome in genus Withania). A large single-copy region (91.285 kb), a small single-copy region (18.373 kb) form the genomic region, and are distinct from each other by a large inverted repeat (22.056 kb). 137 chloroplast genes are found including 4 rRNAs, 38 tRNAs and 83 protein-coding genes. The Withania frutescens chloroplast genome as well as four closest relatives was compared for features such as structure, nucleotide composition, simple sequence repeats (SSRs) and codon bias. Compared to other Withania species, Withania frutescens has unique characteristics. It has the smallest chloroplast genome of any Withania species, isoleucine is the major amino acid, and tryptophan is the minor, In addition, there are no ycf3 and ycf4 genes, fourth, there are only fifteen replicative genes, while in most other species there are more. Using fast minimum evolution and neighbor joining, we have reconstructed the trees to confirm the relationship with other Solanacaea species. The Withania frutescens chloroplast genome is submitted under accession no. ON153173.
... The active ingredients in this herb are steroidal lactones known as withanolides. The most important withanolides found in plant tissues are withaferin A, withanolide A, and withanone (Jayaprakasam & Nair, 2003;Ichikawa et al., 2009;Praveen et al., 2010). The type of plant tissue and the environment in which the plants were raised are two factors that can affect the synthesis of secondary metabolites. ...
Indian ginseng, also known as Withania somnifera, is a popular medicinal plant used as a domestic treatment for a number of age-related illnesses. The field grown WS roots are referred as as a Rasayana (Rejuvenator) medication in the traditional Ayurvedic medicine of India. It has been utilized as the main component in many formulations to help slow down the aging process, manage stress, and be a remarkable neuroprotectant. The quantity and quality of traditionally grown plants, however, provide a considerable hurdle to their use in herbal-based products. The objective of this study was to determine the toxicity of shoots of in vitro developed W. somnifera, in Caenorhabditis elegans model and to compare the toxicological effect with that of plant shoots grown in the field. We found that biosafety is strictly concentration dependent. It was clear from the results that 250 µg/µL of W. somnifera shoot extract exhibited maximum viability for wild type animals.
... Various pharmacological activities are taken from the natural products, including antitumor, antiangiogenic, antiinflammatory, cardioprotective, and immunomodulatory effects [28,29]. Various herbal medicines are prepared for the medication of stress and anxiety, osteoarthritis, immunomodulatory, conjunctivitis, and tuberculosis in which the secondary metabolite used a constituent [30][31][32][33][34]. Various effects possess by these metabolites are antioxidative, immunomodulatory, anti-convulsant, adaptogenic, anticancer, and neurological effects.In the treatment of osteoarthritis, geriatric, behavioral, and anxiety Ashwagandha has been found to be very efficient [2,[35][36][37][38][39][40][41]. ...
India is the world’s richest country, with a vast array of plants and genetic resources for medicinal plants. When
it comes to the introduction of new plant species, environmental factors are crucial. When plants are subjected
to various environmental conditions, they produce tissue-specific secondary metabolites. The main metabolites
are found in varying amounts throughout the medicinal plant’s tissues. With regard to location and environmental
conditions, production of bioactive metabolites plays a critical impact. As a result, the agro-climatic conditions
are favorable for the introduction and domestication of new imported plant types with improved and consistent
contents. Keeping in mind the pharmacological importance of bioactive components, the current chapter focuses
on the hairy root production used to increase their production through the use of new technologies. Keeping in
mind the pharmacological importance of bioactive substances, the current chapter focuses on hairy root formation,
which is aided by rhizosphere modeling through Agrobacterium rhizogenes. In some dicotyledonous plants, soil
bacteria called A. rhizogenes causes hairy root disease. A. rhizogenes-mediated transformation aids in a better
understanding of the rhizosphere’s host-plant association system, as well as the use, transformation, and formation of
new upgrade transgenic crops hairy root culture, which is beneficial for improved growth and continuous production
of pharmacologically bioactive ingredients in elite germplasm.
... ex Batt (Solanaceae) is a wild species growing in Mediterranean areas and has traditionally been used as a cytotoxic, immunomodulatory, analgesic, healing, and anticholinesterase substance. This species is rich in phenols, particularly glycowithanolides and withanolides, along with volatile compounds [14][15][16][17][18][19][20][21]. The current study was designed to investigate the phytochemical composition, antioxidant, and insecticidal properties W. adpressa extract. ...
Withania adpressa Coss. ex Batt is a wild plant belonging to the family Solanaceae, native to the Mediterranean area. The present work was undertaken to study the chemical composition, antioxidant and insecticidal properties of Withania adpressa Coss. ex Batt (W. adpressa) extract. The plant extract was obtained by use of maceration with hydroethanol, and its chemical composition was characterized by use of HPLC. Evaluation of antioxidant potency was achieved by use of DPPH, TAC and FRAP bioassays. Insecticidal activity was tested against Callosobruchus maculatus (C. maculatus) by investigating its mortality, longevity, fecundity and emergence after being immersed with hydroethanol extract of W. adpressa. HPLC analysis revealed that the studied extract is rich in apigenin, luteolin, rutin hydrate, gallic acid, p-coumaric acid, acid gallate, and ferulic acid. The crude extract of W. adpressa recorded excellent antioxidant potencies with calculated values as follows: IC-50 of 49.01 ± 0.65 µg/mL (DPPH), EC50 of 119.61 ± 1.81 µg/mL (FRAP), and 483.47 ± 5.19 µg EAA/mg (TAC). Regarding insecticidal activity, it was revealed that the mortality of C. maculatus after being treated with hydroethanol extract reached 94.21 ± 2.05%. In addition, hydroethanol extract effectively controlled the longevity, fecundity, and the emergence of C. maculatus. The outcome of the present work suggests that W. adpressa derivatives have promising antioxidant and insecticidal properties, and consequently, they may be used as natural insecticides and antioxidants.
... The Withania genus has traditionally been used to control diseases including conjunctivitis, inflammation, anxiety, neurological diseases, bronchitis, ulcers, liver, and Parkinson's disease [9]. Scientific reports mentioned that the Withania genus possessed biological properties such as cytotoxic, immunomodulatory, analgesic, healing, and anticholinesterase [14][15][16][17][18][19][20][21]. W. adpressa (Solanaceae) grows in North Africa and Mediterranean areas, known for its pharmacological properties including immunomodulatory anti-inflammatory effects [22,23]. ...
Withania adpressa (Coss.) Batt. (W. adpressa) is a wild medicinal plant in the family Solanaceae, which is used as an alternative medicine. The present study aims to investigate the chemical composition, antioxidant, and antibacterial potentials of polyphenol-rich fraction from the leaves of W. adpressa. Polyphenol-rich fraction was characterized by use of high-performance liquid chromatography (HPLC). Antioxidant potency was determined by use of 1,1-diphenyl-2-picrylhydrazyl (DPPH), ferric reducing antioxidant power (FRAP), and total antioxidant capacity (TAC) assays. Antibacterial activity was assessed against gram-positive and gram-negative bacteria by use of disc diffusion and microdilution assays. Chromatographic analysis by HPLC showed four compounds in the polyphenol-rich fraction including 1-O-Caffeoyl glucose, Luteolin-7-diglucuronide, Apigenin-O-pentoside, and Quercetin-3-O-glucuronide. Polyphenol-rich fraction exhibited important antioxidant activity as assessed by DPPH and FRAP assays, with IC50 and EC50 values of 14.27 ± 0.43 and 39.48 ± 0.81 µg/mL, respectively, while butylated hydroxytoluene (BHT) and Quercetin exhibited IC50 values of 28.92 ± 0.24 and 22.48 ± 0.54 µg/mL. Results of TAC showed that the polyphenol-rich fraction scored 781.74 ± 2.83 µg AAE/mg. Polyphenol-rich fraction showed an important antibacterial effect vs gram-positive and gram-negative strains recording inhibition zone diameters varying from 19.5 to 29.2 mm, while antibiotics were almost ineffective toward all strains except for E. coli. It can be concluded that W. adpressa polyphenol-rich fraction possesses promising phenols with strong antioxidant and antibacterial properties, which may help fight pathogenic bacteria and free radicals.
... Withanolide A has recently been credited with a neotropic agent for recovery from nervous degeneration dendrites formation and its branching, and hence it can be a promising compound for the treatment of neural degeneration types of disease like Parkinson's and Alzheimer's disease (Kuboyama et al. 2005;Sabir et al. 2011). Other biological activities of W. somnifera include cholinesterase inhibition (Choudhary et al. 2004(Choudhary et al. , 2005, anti-inflammatory via COX-2 enzyme inhibition (Jayaprakasam and Nair 2003), antibacterial activity and sex hormone deficiency regulation (Kiasalari et al. 2009), antiglycation (Maurya et al. 2008), and antipyretic activities (Ali et al. 1997). ...
An improved Agrobacterium rhizogenes-mediated genetic transformation of Withania somnifera (L.) Dunal was developed using the bacterial strain R1000 with leaf segment explants of in vitro raised plantlets. Out of the three strains used (R1000, MTCC 2364 and MTCC 532), the strain R1000 proved to be more efficient than others. Among the different conditions tested, the highest (93.3 %) transformation rate was observed after 3 weeks when the explants were subjected to sonication (15 s) and heat treatment (41°C for 5 min). Transgenic status of the hairy roots was confirmed by PCR using rol B-specific primers. HPLC analysis showed the ability of hairy roots to synthesize withaferin A and withanolide A, both steroidal lactones of medicinal value. This protocol offers new avenue in A. rhizogenes-mediated hairy root induction and is useful for large-scale production of these bioactive compounds from W. somnifera.
... Therefore withanaloide glycans and withanaloides could be the next substitutes of NSAIDs. [36,37,38] Anti-Tumour Activity Withacoagulin A, withacoagulin C, withacoagulin D, withacoagulin E, withanolide L, , withanolide J, Δ3 iso withanolide F, withanolide F, withacoagulin and (22R)-14α15 α17β-20 β, tetrahydroxy-1oxowitha 2,5,24 trien, 26,22-withanolide compounds had relatively good potency on the inhibition of both Con A-induced T cell and LPSinduced B-cell proliferation that, among these compounds, withanolide F proved to have the strongest activity. Withanolides induce apoptosis in HL-60 leukemia cells via mitochondria then the cytochrome C was released and caspase activation. ...
... Studies have shown its several activities against CNS disorders, especially anti-convulsant effects, anti-Alzheimer's activities, nootropic activities, anti-Parkinson's activities, anti-depression activities, anti-anxiety activities, neuroprotective activities, and neuritic regeneration activities. [159,[185][186][187][188] The root is most commonly used part, and the bioactive compounds obtained from the root have shown effectiveness against CNS disorders. Withanoside IV and Withanolide A, which are steroidal lactones, diminished β-amyloid protein which enables the treatment of Alzheimer's disease. ...
Complementary and alternative system of medicine has been at the center of drug discovery for different CNS disorders. Medicinal plants have been in use in healthcare settings and have interestingly fostered the leads for drug development aimed at treating various diseases such as CND disorders, malaria, mycetoma, and inflammation. Electroacupuncture (EA) has the ability to protect prolonged restraint stress, attenuate depressions, and manage few CNS disorders. Bacopa monnieri, Rhodiola rosea, Centella asiatica, Cannabis sativa, Curcuma longa, Cyperus rotundus, Morinda citrifolia, and Withania somnifera are among the most common plants used for treating CNS disorder. Bioactive compounds such as valtrate, curcumin, cannabinoids, apomorphine, pergolide, benzatropine, β-asarone, α-Asarone have been used to treat various CNS disorders, such as addiction, insomnia, depression, Alzheimer’s disease, epilepsy, vitiligo, Parkinson’s disease. These complementary and alternative system of medicines have promising lead in the quest to develop more drugs for CNS disorders.
... The most eminent anti-inflammatory drugs in Ayurveda which also has been scientifically proved Zinziber officinalis [5], Curcuma longa [6], Ajuga bracteosa [7], Boswellia serrata, Withania somnifera [8], Vitex negundo [9], Tripterygium wilfordii [10], Semecarpus anacardium, Aesculus hippocastanum, Bacopa monnieri [11], Cardiospermum halicacabum [12], Tinospora cordifolia [13], Justicia gendarussa [14], Glycyrrhiza glabra [15], Emblica officinalis, Harpagophytum procumbens [16]. Ananus comosus [17], Calopltyllum inophyllum [18], Carum copticum [19], Commiphora wighitii [20], Mangifera indica [21], Pergularia daemia [22], Piper longum [23], Plumbago Zeylanica [24], Ricinus communis [25], Rubia cordifolia are some notable conventional therapeutic plants evidently proved for their antioxidant, anti-inflammatory and antiarthritic properties. ...
Free radicals are unstable, highly reactive molecules, creates oxidative stress in our body by attacking healthy cells and tissue biomolecules. They are usually neutralized by the antioxidant mechanisms in our system. When the antioxidant mechanism fails to stabilize the radicals, we need external antioxidants to protect our cells from oxidative damage. The objective of present study is to evaluate the antioxidant and anti-inflammatory properties of stem and root extracts of the plant Cissus quadrangularis. Stem and root powders of CQ was extracted with different solvent and they were tested against the synthetic free radical DPPH, ABTS, NO, H2O2 and FRAP with the reference standard BHT. The in vitro anti-inflammatory activity assay was also performed for all the extracts along with the reference standard naproxen. The 50 percentage of inhibitory concentration (IC50-μg/ml of extract) values of ethanol fraction from both stem and root extract was found to be in DPPH- (IC50: 32±0.07 & 28±0.02), ABTS- (IC50: 115±0.22 & 120±0.06), NO- (IC50: 13±0.05 & 47±0.13), H2O2- (IC50: 21±0.08 & 28±0.09), TAA- (PI: 73±0.16 & 66±0.22) and the protein denaturation assay showed the ethanol fraction has protective activity levels of 220±0.03 & 277±0.22 in stem and root extracts respectively. Results obtained from this study suggested that both stem and root extracts of CQ possesses potential antioxidant and anti-inflammatory properties.
... The majority of compounds showed selective COX-2 enzyme inhibition suggesting their anti-inflammatory activity. 36 The hydro-methanolic extract in stainless steel implant induced inflammation in zebrafish invivo model has shown an inhibitory effect of TNF α. 37 The root part of W. somnifera finds its usage more in experimental models as well as in clinical practice. Hydroalcoholic root extract showed anti-inflammatory effect by inhibition of protein (albumin) denaturation in the in-vitro model. ...
... 4-Deoxywithaperuvin isolated from alcoholic fruit extract was characterized by spectral analysis and found to contain five hydroxyl moieties (at 5, 6, 14, 17, and 20 positions) (72). Viscosalactone B in the alcoholic extract of the whole plant was investigated as a structural analog of withaferin A having an epoxy group at 6 and 7 positions, double bond at C-24, and three hydroxyl groups at 3, 4, and 27 positions of carbon skeleton (73). Withanolide Y was identified as 5α, 6α-epoxy-7α, 17α, 20R-trihydroxy-1-oxo-22R-witha-2, 24-dienolide using single-crystal XRD (74). ...
Withania somnifera L. is a multipurpose medicinal plant of family Solanaceae occurring abundantly in sub-tropical regions of the world. The folk healers used the plant to treat several diseases such as fever, cancer, asthma, diabetes, ulcer, hepatitis, eyesores, arthritis, heart problems, and hemorrhoids. The plant is famous for the anti-cancerous activity, low back pain treatment, and muscle strengthening, which may be attributed to the withanolide alkaloids. W. somnifera is also rich in numerous valued secondary metabolites such as steroids, alkaloids, flavonoids, phenolics, saponins, and glycosides. A wide range of preclinical trials such as cardioprotective, anticancer, antioxidant, antibacterial, antifungal, anti-inflammatory, hepatoprotective, anti-depressant, and hypoglycemic have been attributed to various parts of the plant. Different parts of the plant have also been evaluated for the clinical trials such as male infertility, obsessive-compulsive disorder, antianxiety, bone and muscle strengthening potential, hypolipidemic, and antidiabetic. This review focuses on folk medicinal uses, phytochemistry, pharmacological, and nutrapharmaceutical potential of the versatile plant.
... Various uses of this species including nervous system disorders (tonic, senile debility, nervous tension, loss of memory) reflect the ethnopharmacological importance. Recent studies also demonstrated its multiple activities on nervous system disorders, particularly neuritic regeneration activity [72], neuroprotective activity [73], anti-anxiety and anti-depression activity [74], anti-Parkinson's activity [75], nootropic and anti-Alzheimer's activity [76], and anti-convulsant effects [77]. Roots are the most frequently used parts and the compounds isolated from these roots are effective against nervous system disorders. ...
The majority of the population in Bangladesh uses traditional plant-based medicines to manage various ailments, including central nervous system (CNS) disorders. This review presents ethnobotanical information and relevant scientific studies on plants used in traditional healthcare for the management of various CNS disorders in Bangladesh. The information on the medicinal plants of Bangladesh effective against CNS disorders published in scientific journals, books, and reports was compiled from different electronic databases using specific key words. The present article provides comprehensive information on a total of 224 medicinal plant species belonging to 81 families used for the treatment of CNS disorders by the various peoples of Bangladesh. In total, we reviewed more than 290 relevant papers. In this study, leaves were found as the most often used plant organ, followed by roots, fruits, whole plants, barks, seeds, stems, rhizomes, and flowers. The Fabaceae family contributes the highest number of used species, followed by Rubiaceae, Lamiaceae, Cucurbitaceae, Vitaceae, Euphorbiaceae, Malvaceae, and Zingiberaceae. The most frequently used species (in decreasing order) are Asparagus racemosus, Centella asiatica, Stephania japonica , Aegle marmelos, Coccinia grandis, Tabernaemontana divaricata , Bacopa monnieri , Abroma augusta, and Scoparia dulcis . This review may serve as a starting point for a rational search for neuroactive natural products against CNS disorders within the Flora of Bangladesh.
Graphic Abstract
... W. frutescens has been widely used by the indigenous population against intoxication [4], as other studies reported their pharmacological properties (antioxidant, antimicrobial, and antifungal) [5]. Genus Withania is widely used in traditional medicine for the treatment of stress, inflammation, conjunctivitis, tuberculosis, and many other infections [6][7][8][9][10] and exhibited immunomodulatory effects on animal models as reported in the earlier data [11][12][13][14][15]. To the best of our knowledge, no early literature investigated the toxicity assessment of W. frutescens and therefore the current research was undertaken to screen its phytochemical composition as well as its toxicological profile in mice. ...
Background:
Withania frutescens. L (W. frutescens) is a perennial woody medicinal plant belonging to family Solanaceae largely used by the indigenous population to Morocco for the treatment of disease.
Objective:
The purpose of this study was to investigate the chemical composition, acute, and subacute toxicity of W. frutescens extract in mice.
Materials and methods:
The phytochemical composition of W. frutescens extract was determined using a gas chromatograph (GC/MS). Acute toxicity study was carried out in mice through oral administration of single doses 500 mg/kg, 1000 mg/kg, and 2000 mg/kg for 14 days. Subacute toxicity was performed with oral administration of repeated doses 500 and 2000 mg/kg/day for 28 days. Biochemical parameters (alanine aminotransferase, aspartate aminotransferase, urea, and creatinine), as well as histopathological changes potentially occurred in organs, (liver, kidney, and spleen) were evaluated.
Results:
The results of chromatographic analysis showed the richness of W. frutescens extract in interesting phytochemical compounds majorly constituted of bicyclo[3.1.1]heptane, 6,6-dimethyl-2-methylene-(C10H16). Regarding acute toxicity study, the results showed no clinical symptoms occurred in treated mice compared to the control group and no histological changes detected in analyzed organs of treated mice with dose put to 2000 mg/kg nor adverse effect on biochemical parameters.
Conclusion:
The outcome of this work showed no toxic effect of W. frutescens in mice up to dose 2000 mg/kg bodyweight. Therefore, this study could scientifically validate further traditional use with safety in the range of tested doses.
... Apart from this, Withanolide A having cholinesterase inhibitory property (Chen et al. 2011), where as Withanolide D has been reported to be antitumor and antimetastatic by Leyon and Kuttan (2004). Withangulatin A exerts immunosuppressive effects (Sun et al. 2005), whereas Viscosalactone B displays anti-inflammatory property (Jayaprakasam and Nair 2003). ...
Since the origination of human society, natural products and their derivatives especially obtained from medicinal plants have been used for the advantage of mankind due to their precious therapeutic potential. In Indian Ayurveda, different types of plant-based products have been used to cure several human diseases without any significant side effects, and that’s why an effective number of modern medicines has been isolated from natural sources involving medicinal plants. There are still some disease conditions where only synthetic drugs can be used for the treatment which quite often may lead to mild or severe side effects. It is, therefore, necessary to explore chemical compounds from Indian traditional medicinal plants as viable substitutes to the synthetic drugs in order to overcome their adverse effects and also the exorbitant cost. Glucocorticoids are widely used as potent anti-inflammatory and immunosuppressive agents for the treatment of various complications such as rheumatoid arthritis, joint pain, dermatitis, asthma, allergy, etc. Unfortunately, long-term use of corticosteroids even in low amount may cause severe adverse effects such as osteoporosis, reduction in bone mass, overweight, cataract–glaucoma, blurred vision, aggression, agitations, psychiatric and cognitive disturbance, cardiovascular disorders, hyperlipidemia, growth suppression, and many more. It has therefore been realized to explore plant-based principles as alternative and complementary therapeutics with almost no toxicity. The phyto-steroids such as solasodine, diosgenin, boswellic acid, glycyrrihizin, guggulsterones, withnolides, or sarsasapogenin are reported to have structural similarity with glucocorticoids or glycosides. In addition, the saponins, lactones, and some aliphatic compounds have been reported to possess efficiency to cure those diseases in which steroids are employed. However, extensive research is needed to detect other phytochemicals which may prove to act as potential substitutes of synthetic steroidal drugs. In this chapter, we have made an endeavor to present an updated account of those medicinal plants and corresponding phytochemicals with varied therapeutic properties as effective alternative steroids to be used against different chronic diseases.
... This may prove particularly valuable in the management of neuropsychiatric disorders. With regard to its therapeutic mechanisms, neuroinflammation (Na, Jung, & Kim, 2014) and immune dysfunction (Van Kesteren et al., 2017) are implicated in the pathogenesis of numerous neuropsychiatric illnesses, and extracts containing W. somnifera have been shown to strongly inhibit cyclooxygenase-2 enzyme (Jayaprakasam & Nair, 2003), reduce the levels of serum acute-phase reactants (Anbalagan, 1982), and suppress α2-macroglobulin (Anbalagan & Sadique, 1984), thereby attenuating systemic inflammation. This may be attributed to the rich steroidal lactone content of W. somnifera. ...
Many developed countries are experiencing a rapidly “greying” population, and cognitive decline is common in the elderly. There is no cure for dementia, and pharmacotherapy options to treat cognitive dysfunction provide limited symptomatic improvements. Withania somnifera (Ashwagandha), a popular herb highly valued in Ayurvedic medicine, has often been used to aid memory and cognition. This systematic review thus aimed to evaluate the clinical evidence base and investigate the potential role of W. somnifera in managing cognitive dysfunction. Using the following keywords [withania somnifera OR indian ginseng OR Ashwagandha OR winter cherry] AND [brain OR cognit* OR mental OR dementia OR memory], a comprehensive search of PubMed, EMBASE, Medline, PsycINFO and Clinicaltrials.gov databases found five clinical studies that met the study's eligibility criteria. Overall, there is some early clinical evidence, in the form of randomized, placebo‐controlled, double‐blind trials, to support the cognitive benefits of W. somnifera supplementation. However, a rather heterogeneous study population was sampled, including older adults with mild cognitive impairment and adults with schizophrenia, schizoaffective disorder, or bipolar disorder. In most instances, W. somnifera extract improved performance on cognitive tasks, executive function, attention, and reaction time. It also appears to be well tolerated, with good adherence and minimal side effects.
... Herbalists criticize the manner in which many scientific studies make insufficient use of historical knowledge, which has been shown useful in drug discovery and development in the past and present (Ammon et al. 1993). They maintain that this traditional knowledge can guide the selection of factors such as optimal dose, species, time of harvesting and target population (Jayaprakasam and Muraleedharan 2003). ...
Since the ancient period, the medicinal plants have been used in pharmaceutical and cosmetic industries. Recently, it has gained extreme research importance for their nutraceuticals values. It has been confirmed by WHO that herbal medicines serve the health needs of about 80% of World’s population; especially for millions of people in the vast rural areas of developing countries. This book chapter summarizes the importance of several medicinal plants which are traditionally used in treatment and management of different ailments in India. In addition, some pharmacological models describe the possible mechanism of action of bioactive phytochemicals, which can be successfully used as drug candidates in near future. However, there is urgent need for basic scientific investigations on medicinal plants and this has been highlighted in current research trends in clinical trials.
... Moisture, Ash, Protein, Fat, Crude fiber were determined in proximate analysis. The Carbohydrate determined by differences [5,6] . ...
Stress and fast life is major cause of many diseases. Withania somnifera is herb rich in micronutrient which reduce stress and depression. The Aim of present study is to formulate cookies enrich with wethania somnifera herb. The value added cookies samples were prepared in four different ratio and combination. W0, WC1, WC2 and WC3. Each experiment was replicated five times. The sensory value was determined by 9-point hedonic scale of 10 panel judge's expert in food technology. Nutritional and proximate value were determined by AOAC method (2010) all data were statistical analyzed using standard deviation techniques. The sensory value of different cookies reflects.
... These compounds were mainly discovered in plants of the genus Solanum (Solanaceae) 1- 19 and in few marine organisms. 20,[21][22][23] Previous studies on withanolides have proven their wide spectrum of biological activities, including phytotoxic activities, 1 cytotoxic, 12,18,21,22,24,25 anti-inflammatory, 7,11,14,23 anti-microbial, 26 chemopreventive, 27 and antiviral activities. 19 Although the genus Solanum has been unveiled to produce bioactive withanolides, there are few reports about the chemical constituents of S. capsicoides (syn. ...
A phytochemical investigation of the leaves of Solanum capsicoides resulted in the isolation and characterization of five new withanolide-type steroids, capsisteroids G–K (1–5), along with three known analogues (6–8). Their structures were identified by interpretation of the NMR and HRESIMS data as well as by spectral data comparison with known analogues. The isolated steroids were found to be not cytotoxic against a limited panel of cancer cell lines. The ability of the isolated steroids to suppress superoxide anion generation and elastase release in N-formyl-methionyl-leucyl-phenylalanine/cytochala-sin B (fMLF/CB)-induced human neutrophils was also evaluated and displayed variable activities.
The aim of this review paper was to summarize some commonly available plants which have anti-inflammatory activity with their phytochemical constituents. The data were collected from Current Contents and Scientific Journals, which included in publications. In this paper, the plants have anti-inflammatory activity along with their phytochemical constituents and also mention the family, part used of the every plants. Herbal plants play a significant role in human health in relation to the prevention and treatment of inflammatory conditions. Herbal medicines are popular among the public and improvements in their formulation have resulted in a new generation of phytomedicines that are more potent than before. This paper highlights on the phytochemical constituents of anti-inflammatory activity of some herbal medicines used for treating inflammatory disorders and recent developments in various herbal species. The review gives a comprehensive overview of the phytochemical constituents of medicinal plants with anti-inflammatory potential.
This article presents a comprehensive overview of recent discoveries and advancements in the field of steroid chemistry, highlighting the isolation and characterization of various steroidal compounds from natural sources. This paper discusses a wide range of steroids, including pregnane steroids, steroidal alkaloids, ketosteroids, and novel triterpenoids, derived from marine organisms, fungi, and plants. Significant findings include the isolation of bioactive compounds such as the cytotoxic erectsterates from microorganisms, soft corals, the unusual tetracyclic steroid penicillitone from a fungal culture, and innovative steroidal derivatives with potential anti-inflammatory and anticancer activities. The synthesis of steroids from microorganisms as a tool for pharmaceutical development is also explored, showcasing the role of microbial biotransformation in generating steroidal drugs. Additionally, this paper emphasizes the ecological and medicinal relevance of these compounds, which are often used in traditional medicine and have potential therapeutic applications in treating diseases like cancer and microbial infections. This article serves as a vital resource for researchers interested in the chemical diversity of steroids and their applications in drug discovery and development.
Purpose
This review paper delves into the comprehensive understanding of Ashwagandha, spanning its botanic occurrence, conventional applications, extraction techniques and pivotal role in addressing various disorders.
Design/methodology/approach
Introduction Ashwagandha, also known as Withania somnifera, is a remarkable botanical resource with a rich history of use in traditional medicine.
Findings
In botany, Withania somnifera thrives in diverse ecosystems, particularly in tropical and subtropical regions. Its extensive distribution across regions, the Canary Islands, South Africa, the Middle East, Sri Lanka, India and China underscores its adaptability and resilience. The traditional uses of Ashwagandha in Ayurvedic and indigenous medicine systems have persisted for over 3,000 years. With over 6,000 plant species utilized historically, India, often regarded as the “botanical garden of the world,” has firmly established Ashwagandha as a cornerstone in traditional healing practices.
Originality/value
Extraction methods play a pivotal role in harnessing the therapeutic potential of Ashwagandha. Ultrasonic-assisted extraction and high-performance liquid chromatography are among the techniques employed to obtain the key bioactive compounds. Ashwagandha’s significance in modern medicine is underscored by its potential to address a spectrum of health issues. The multifaceted bioactivity of Ashwagandha is attributed to its antioxidant, anti-inflammatory, heart conditions, metabolic disorders, renal ailments, hepatic diseases and adaptogenic properties, making it a subject of increasing interest in contemporary medical research. This review synthesizes the assorted perspectives of Ashwagandha, from its botanical roots and conventional employments to its advanced extraction strategies and its intention to basic well-being challenges, advertising important bits of knowledge for analysts, specialists and healthcare experts alike.
Shrikhand is a popular Indian dairy dessert prepared by the fermentation of buûalo milk. It is manufactured from breaking of curd called as chakka and then mixing with other ingredients. Ashwagandha root extract has been added by optimization for manufacturing of Ashwagandha root extract modulated shrikhand. Since this medicinal plant has immunomodulataory properties, we can call our product as 'immunodulatory shrikhand'. Sensory and textural parameters were analyzes in the manufactures sample and was observed that it varies significantly and quite acceptable by the semi-trained panels.
The present experiment was carried out at College farm, N.M. College of Agriculture, Navsari Agricultural University,Navsari. During the year 2011-2012, to investigate the Weed management in sunflower (Helianthus annuus L.) under South Gujarat condition. Ten treatments comprising combination of pre-(Pendimethalin & Alachlor) and post-emergence (Quizalofop-ethyl & Imazethapyr) herbicides including weed
free and weedy check were tested in randomized block design with three replications. Pre-mergence application of Pendimethalin either 1.0 kg ha-1 or Alachlor 1.0 kg ha-1 were found effective to control different weed species. Hand
weeding & IC at 20 and 40 DAS weed free condition was proved effective against all weed species. Being equivalent to hand weeding & IC at 20 and 40 DAS, maximum seed and stover yields of sunflower were recorded under pre-emergence application of Pendimethalin @ 1 kg ha-1 pre-emergence + hand weeding at 20 and 40 DAS. Similarly, tend was found in yield attributes parameter viz., number of seed per head, seed weight per head, 100-seed weight and quality of protein yield.
And also nutrient content & uptake was recorded by crop.Application Alachlor @ 1 kg ha-1 pre-emergence + hand weeding at 20 and 40 DAS and Alachlor @ 1 kg ha-1 preemergence reflected in higher B:C ratio of 4.16 and 3.85, respectively.
Leishmaniasis is a group of infectious diseases caused by Leishmania protozoa. The ineffectiveness, high toxicity, and/or parasite resistance of the currently available antileishmanial drugs has created an urgent need for safe and effective leishmaniasis treatment. Currently, the molecular-docking technique is used to predict the proper conformations of small-molecule ligands and the strength of the contact between a protein and a ligand, and the majority of research for the development of new drugs is centered on this type of prediction. Leishmania N-myristoyltransferase (NMT) has been shown to be a reliable therapeutic target for investigating new anti-leishmanial molecules through this kind of virtual screening. Natural products provide an incredible source of affordable chemical scaffolds that serve in the development of effective drugs. Withania somnifera leaves, roots, and fruits have been shown to contain withanolide and other phytomolecules that are efficient anti-protozoal agents against Malaria, Trypanosoma, and Leishmania spp. Through a review of previously reported compounds from W. somnifera-afforded 35 alkaloid, phenolic, and steroid compounds and 132 withanolides/derivatives, typical of the Withania genus. These compounds were subjected to molecular docking screening and molecular dynamics against L. major NMT. Calycopteretin-3-rutinoside and withanoside IX showed the highest affinity and binding stability to L. major NMT, implying that these compounds could be used as antileishmanial drugs and/or as a scaffold for the design of related parasite NMT inhibitors with markedly enhanced binding affinity.
In the era of COVID pandemic, it is highly desirable to improve body’s immune responses. Many of the diseases including COVID impact the immune system and make it defenseless. There is a growing interest of herbal medicine around the world owing to effective pharmacological actions attributed by its unique phytocompounds. Majority of the immunomodulatory drugs including both immunosuppressor and immuno-stimulators are synthetic organic compounds having side effects. Therefore, there is a growing interest to use plant-based products to regulate immune responses. The present chapter deals with the recognition of members of the family Solanaceae for their use as potential immunomodulators. There are quite a few reports of active phytocompounds isolated from different solanaceous plants that have a myriad of medicinal properties. Various phytochemicals such as phenolic compounds, flavonoids, alkaloids, terpenes, lactones, and glycosides have been shown to have various therapeutic effects on human body owing to their ability to influence body’s immune system. The present chapter will give a comprehensive overview of plant-based therapeutics of solanaceous plants including withanolides isolated from Withania somnifera and Physalis sps, capsaicinoids isolated from Capsicum, and lycopene from tomato. Solanaceae is one of the superfamily having huge repertoire of plants belonging to major food crops utilized throughout the world (tomato, potato, capsicum etc.) as well as in medicine category. Besides several members of the Solanaceae family such as Physalis sps, Atropa sps, Datura stramonium, and Solanum xanthocarpum have potential phytomolecules belonging to alkaloids, terpenoids, and steroid category, which are recognized as medicines. This chapter will also give a critical overview of the possibilities, facts, and prospects of the use of members of Solanaceae family as potential future immunomodulatory drugs.KeywordsSolanaceaeAtropa spsHyoscyamus spsPhysalis sps
Withania somnifera
CapsicumWithanolidesCapsaicinoids
Coronavirus disease 2019 (COVID-19) pandemic has killed huge populations throughout the world and acts as a high-risk factor for elderly and young immune-suppressed patients. There is a critical need to build up secure, reliable, and efficient drugs against to the infection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. Bioactive compounds of Ashwagandha [Withania somnifera (L.) Dunal] may implicate as herbal medicine for the management and treatment of patients infected by SARS-CoV-2 infection. The aim of the current work is to update the knowledge of SARS-CoV-2 infection and information about the implication of various compounds of medicinal plant Withania somnifera with minimum side effects on the patients’ organs. The herbal medicine Withania somnifera has an excellent antiviral activity that could be implicated in the management and treatment of flu and flu-like diseases connected with SARS-CoV-2. The analysis was performed by systematically re-evaluating the published articles related to the infection of SARS-CoV-2 and the herbal medicine Withania somnifera. In the current review, we have provided the important information and data of various bioactive compounds of Withania somnifera such as Withanoside V, Withanone, Somniferine, and some other compounds, which can possibly help in the management and treatment of SARS-CoV-2 infection. Withania somnifera has proved its potential for maintaining immune homeostasis of the body, inflammation regulation, pro-inflammatory cytokines suppression, protection of multiple organs, anti-viral, anti-stress, and anti-hypertensive properties. Withanoside V has the potential to inhibit the main proteases (Mpro) of SARS-CoV-2. At present, synthetic adjuvant vaccines are used against COVID-19. Available information showed the antiviral activity in Withanoside V of Withania somnifera, which may explore as herbal medicine against to SARS-CoV-2 infection after standardization of parameters of drug development and formulation in near future.
Withania aristata (Aiton) Pauquy, a medicinal plant endemic to North African Sahara, is widely employed in traditional herbal pharmacotherapy. In the present study, the chemical composition, antioxidant, antibacterial, and antifungal potencies of extract from the roots of Withania aristata (Aiton) Pauquy (RWA) against drug-resistant microbes were investigated. Briefly, RWA was obtained by maceration with hydro-ethanol and its compounds were identified by use of high-performance liquid chromatography (HPLC). The antioxidant activity of RWA was determined by use of ferric-reducing antioxidant power (FRAP), 1,1-diphenyl-2-picrylhydrazyl (DPPH), and total antioxidant capacity (TAC). The evaluation of the antimicrobial potential of RWA was performed against drug-resistant pathogenic microbial strains of clinical importance by use of the disc diffusion agar and microdilution assays. Seven compounds were identified in RWA according to HPLC analysis, including cichoric acid, caffeic acid, apigenin, epicatechin, luteolin, quercetin, and p-catechic acid. RWA had excellent antioxidant potency with calculated values of 14.0 ± 0.8 µg/mL (DPPH), 0.37 ± 0.08 mg/mL (FRAP), 760 ± 10 mg AAE/g (TAC), and 81.4% (β-carotene). RWA demonstrated good antibacterial potential against both Gram-negative and Gram-positive bacteria, with inhibition zone diameters ranging from 15.24 ± 1.31 to 19.51 ± 0.74 mm, while all antibiotics used as drug references were infective, except for Oxacillin against S. aureus. Results of the minimum inhibitory concentration (MIC) assay against bacteria showed that RWA had MIC values ranging from 2.13 to 4.83 mg/mL compared to drug references, which had values ranging from 0.031 ± 0.003 to 0.064 ± 0.009 mg/mL. Similarly, respectable antifungal potency was recorded against the fungal strains with inhibition zone diameters ranging from 25.65 ± 1.14 to 29.00 ± 1.51 mm compared to Fluconazole, used as a drug reference, which had values ranging from 31.69 ± 1.92 to 37.74 ± 1.34 mg/mL. Results of MIC assays against fungi showed that RWA had MIC values ranging from 2.84 ± 0.61 to 5.71 ± 0.54 mg/mL compared to drug references, which had values ranging from 2.52 ± 0.03 to 3.21 ± 0.04 mg/mL. According to these outcomes, RWA is considered a promising source of chemical compounds with potent biological properties that can be beneficial as natural antioxidants and formulate a valuable weapon in the fight against a broad spectrum of pathogenic microbes.
Phytochemical studies on the aerial parts of Withania somnifera L. Dunal. (Solanaceae) led to the isolation of a chlorinated steroidal lactone (27-acetoxy-4b,6a-dihydroxy-5b-chloro-1-oxowitha-2,24-dienolide), a diepoxy withanolide (5b,6b,14a,15a-diepoxy-4b,27-dihydroxy-1-oxowitha-2,24-dienolide), and withaf-erin A. Their structures were elucidated by using spectroscopic techniques. All three compounds exhibited a growth inhibition and cytotoxic activity against human lung cancer cell line (NCI-H460), with withaferin A being the most potent (GI 50 = 0.18 lg/mL and LC 50 = 0.45 lg/mL) among three compounds tested.
Ashwagandha (W. somnifera L) is a popular ethnomedicinal herb endowed with potential pharmacotherapeutic properties. In this study the ethanol extract (EE) and water extract (WE) of ashwagandha roots were qualitatively analysed using high performance liquid chromatography (HPLC), the results showed EE containing withanoside IV (a), physagulin D (b), 27-hydroxywithanone (c), withanoside V (d), withaferin A (e), withastramonolide (f), withanolide A (g), withanone (h), and withanolide B (i) as major bioactive compounds. Antioxidant potential was studied using four in vitro free radical scavenging assays and EE displayed higher antioxidant effect compared to WE for all assays. The EE also showed enzyme inhibitory effect against lipoxygenase (5-LOX) >cyclooxygenases-1 (COX-1) compared to cyclooxygenases-2 (COX-2) and to that of WE. Furthermore, EE demonstrated a potential cytotoxic effect on proliferation of A549 cells in vitro, showing IC50 values, 394.8 (24 h), 171.9 (48 h) and 126.1 (72 h) μg/mL, respectively. EE extract also exhibited induction of apoptosis in dose dependent manner confirmed with the production of ROS in A549 cells through flow cytometric analysis. The obtained results demonstrated that ashwagandha EE with high concentration of bioactive compounds could act as potential drug candidates against pro-inflammatory enzymes involved in development of inflammation and progression of lung cancer. Further, extensive research is needed to investigate the ashwagandha bioactive compounds responsible for treating inflammation, oxidative stress and lung cancer.
Background: Datura stramonium L. is widely used across the world for its therapeutic potential to treat inflammatory disorders. The current work was designed to isolate and identify steroidal lactones from D. stramonium leaves and evaluate their anti-inflammatory and analgesic properties.
Methods: Several compounds were isolated from D. stramonium leaves and characterized by nuclear magnetic resonance and high-resonance electron spray ionization mass spectrometry techniques. Further, anti-inflammatory properties of these compounds were evaluated by in vitro assays, such as release of NO and pro-inflammatory cytokines by lipopolysaccharide (LPS)-activated J774A.1 macrophages. Using in vivo models, anti-inflammatory and analgesic effects were examined by mouse tail-flick, carrageenan-induced inflammation in rat paw model, vascular permeability in rats, and acetic acid-induced writhing in mice. The docking studies were performed for assessing the binding efficiency of the test compounds with cyclooxygenase-1 (COX-1) and COX-2, lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1), inducible nitric oxide synthases (iNOS) and nuclear factor-κB (NF-κB).
Results: Three lactones were isolated and confirmed as daturalactone (D1), 12-deoxywithastramonolide (D23), and daturilin (D27). Further, the isolated compounds showed nitric oxide inhibition and pro-inflammatory cytokines released by LPS-activated J774A.1 macrophages. The in vivo results suggest that D1, D23 and D27 (20 mg/kg) were able to reduce the pain and inflammation in various animal models. The docking analysis showed that these three compounds actively bind with COX-1, COX-2, LOX-1, NF-κB, and iNOS, validating the anti-inflammatory effects of the lactones.
Conclusion: These findings demonstrate substantial anti-inflammatory and analgesic properties of D. stramonium-derived lactones and their potential as anti-inflammatory agents to treat chronic inflammatory ailments.
Balarista, a classical ayurvedic formulation, is traditionally claimed for the treatment of rheumatoid arthritis (RA). The drawback behind this fermented product remains lack of its proper documentation and validation. In the present investigation, therefore, an in-house Balarista (IBF) formulation was prepared by using standard raw materials as mentioned in API (Ayurvedic Pharmacopoeia of India). As the preclinical scientific data regarding its molecular mechanism of action were not evaluated, so the present work was undertaken to investigate its anti-arthritic potential using Complete Freund's adjuvant (CFA) induced arthritic rat model and was compared with the marketed (AVS, BD, DB, RN) formulations. Rats were immunized by injecting CFA of 0.1 ml into the sub-plantar surface of right posterior paw. Animals were treated with formulation (2.31 ml/kg) and indomethacin (1 mg/kg) for 28 days and were sacrificed on 29th day. The hematological and biochemical parameters were studied. The histology and x-ray analysis were performed on proximal interphalangeal joints of the experimental rats. The molecular docking of the constituents identified from GC-MS analysis of IBF formulation was carried out with COX-2 receptor to find out the interaction using celecoxib as standard. The quantification of vasicine and total withanolides was performed by HPLC analysis for their standardization. A significant decrease in paw diameter, arthritic index and histological score was noticed in formulation treated groups. The decrease in body weight and alteration in hematological and biochemical parameters were also significantly checked by the IBF and marketed formulation in contrast to CFA treated groups. Remarkable reduction of TNF-α, IL-1β, and IL-6 were noticed in all the formulation treated rats. The histological study revealed decrease in synovial hyperplasia, pannus formation, and cartilage and bone erosion. The X-ray analysis showed decrease in soft tissue swelling, bone resorption and osteophyte formation upon the treatment with formulations. Based on docking score the components, 8-Azaspiro[4.5]decane-7,9-dione (-7.5); (3aS,7aR)-5,6,7a-trimethyl-4,7-dihydro-3aH-2-benzofuran-1,3-dione (-7.5); 2,6-Ditert-butylphenol (-7.2) exhibited significant binding affinity. The prophylactic activity of the formulation could be due to the synergistic effects produced by the phyto-constituents identified by GC-MS analysis. Moreover, the anti-arthritic activity of the IBF was attributed by the predominance of withaferin A.
Cancer is a leading cause of mortality worldwide, the conventional chemotherapeutic drugs have been known for their toxicity and numerous side effects. A new approach to treat cancer involves phytochemical drugs. In the present review, anti-cancer activity of a class of steroidal lactones called withanolides obtained from Withania somnifera (L.) Dunal is discussed. The commonly studied bioactive compounds namely withaferin-A, withanoside IV, withanoside VI and withanolide-A among others obtained from methanolic and chloroform extract of the leaves and various alcoholic, aqueous and chloroform extract of roots have shown inhibition to various human cancer cell lines including skin, breast, colon, prostate, liver, ovary, cervical and lung. Prominent mechanisms of action include induction of apoptosis by NOS upregulation, ROS production and NBS2 or COX-2 inhibition; cytotoxicity by humoral and cell mediated immune response, activation of p53 and pRB and inhibition of various viral oncoproteins; cell cycle arrest by Cdc2 facilitated mitotic catastrophe, cyclin-D1 down-regulation and inhibition of transcription factors. Cancers are also controlled by inhibition of angiogenesis and metastasis of the tumor cells. In addition to anti-tumorogenic properties, W. somnifera also holds properties that make it a potential adjuvant in integrated cancer therapeutics and in enhancing the effectiveness of ongoing radiation therapy.
Cancer is a leading cause of mortality worldwide, the conventional chemotherapeutic drugs have been known for their toxicity and numerous side effects. A new approach to treat cancer involves phytochemical drugs. In the present review, anti-cancer activity of a class of steroidal lactones called withanolides obtained from Withania somnifera (L.) Dunal is discussed. The commonly studied bioactive compounds namely withaferin-A, withanoside IV, withanoside VI and withanolide-A among others obtained from methanolic and chloroform extract of the leaves and various alcoholic, aqueous and chloroform extract of roots have shown inhibition to various human cancer cell lines including skin, breast, colon, prostate, liver, ovary, cervical and lung. Prominent mechanisms of action include induction of apoptosis by NOS upregulation, ROS production and NBS2 or COX-2 inhibition; cytotoxicity by humoral and cell mediated immune response, activation of p53 and pRB and inhibition of various viral oncoproteins; cell cycle arrest by Cdc2 facilitated mitotic catastrophe, cyclin-D1 down-regulation and inhibition of transcription factors. Cancers are also controlled by inhibition of angiogenesis and metastasis of the tumor cells. In addition to anti-tumorogenic properties, W. somnifera also holds properties that make it a potential adjuvant in integrated cancer therapeutics and in enhancing the effectiveness of ongoing radiation therapy.
Plant steroids constitute a diverse group of natural products. Biosynthetically, they are derived from S‐squalene‐2,3‐epoxide via acetate‐mevalonate pathway. Among the plant steroids, phytosterols are ubiquitous in the plant kingdom and some of them are reported to possess hypocholesterolemic activity. Withanolides are a large group of steroidal lactones with various biological activities. Brassinosteroids are a small group of plant steroids classified as plant growth hormones. Phytoecdysteroids are polyhydroxylated plant steroids, many of which are known to exhibit anabolic effects with no undesirable side effects. Steroidal alkaloids are nitrogen‐containing plant steroids with an array of biological activities. It is noteworthy that trace amounts of cholesterol and mammalian steroidal hormones including progesterone have been detected in some plants. Analyses of plant steroids mainly utilize chromatographic methods such as thin‐layer chromatography (TLC), high‐performance liquid chromatography (HPLC), ultra‐high‐performance liquid chromatography (UHPLC), and gas‐liquid chromatography (GLC). In general, photodiode array (PDA), evaporative light scattering (ELS), and fluorescence (FL) detectors and mass spectrometry (MS) are commonly used for detection, quantification, and identification of plant steroids. UHPLC hyphenated with tandem mass spectrometry (MS/MS) has recently become the state‐of‐the‐art method of choice for the analysis of plant steroids, especially for the ones that are present in minor quantities such as brassinosteroids and phytoecdysteroids. Some less common techniques employed for the analyses of plant steroids are immunoassays and biological assays.
Background:
Withanolide glycosides in Ashwagandha (Withania somnifera), are important metabolites attributed with widely acclaimed therapeutic potential for which validated methods for quantitative determination are limited.
Objective:
The primary objective was to develop and validate a Reversed-Phase High Performance Liquid Chromatography (RP-HPLC) method for simultaneous quantification of total withanolide glycosides (WG), withanoside IV and withaferin A present in ashwagandha extract.The study also aimed to identify various other constituents present in the extract.
Method:
Aqueous methanol extract (AME) of ashwagandha was prepared and fractionated into two viz. flavonoid rich fraction (FF) and withanolide rich fraction (WF). RP-HPLC method was developed and validated for estimation of total WG in ashwagandha extract according to ICH guidelines. Preparative HPLC based purification of major compounds from WF fraction was carried out and constituents were identified using spectroscopic techniques. HPLC chemical profiling of WF before and after acid hydrolysis under controlled conditions were carried out to further confirm the glycosidic compounds.
Results:
The RP-HPLC method gave a precise differentiation of flavonoids, withanolides and WG present in ashwagandha extract. The method demonstrated good reliability and sensitivity, and can be conveniently used for the quantification of total WG, withanoside IV and withaferin A present in ashwagandha extracts. According to this method, purified fraction (WF) prepared from roots and leaves of ashwagandha comprise 35 % of total WG, 3.27 % of withanoside IV and 2.40 % of Withaferin A. The method was also applied to different products prepared from ashwagandha with total withanolide glycosides ranged from 1.5 % to 60 % and the results were found to be reproducible. Identification of the individual chemical constituents as well as the acid hydrolytic pattern of the extract further supported the reliability of developed method for the quantitative determination of total WG. This study also reported a new withanolide glycoside named, cilistol V-6’-O-glucoside (Aswanoside) along with some other known withanolide glycosides.
Conclusion:
A Reversed-Phase High Performance Liquid Chromatography (RP-HPLC) method was developed and validated for quantitative determination of total WG, withanoside IV and withaferin A present in ashwagandha extract according to ICH guidelines. This study also reported a new withanolide glycoside named, cilistol V-6’-O-glucoside (Aswanoside) along with some other known WG.
Withania somnifera is a very unique medicinal plant explored by number of orthodox medicinal systems such as Ayurveda, Siddha and Unani. It is commonly known as Ashwagandha, Indian ginseng and winter cherry, and finds its potential medicinal properties in the Ayurvedic Pharmacopoeia of India and Siddha Pharmacopoeia of India. The Withania genus is classified under the Solanaceae family and includes around 60 species, among which W. somnifera and W. coagulans are often mentioned in Ayurveda. Ashwagandha is a treasure house of widespread array of metabolites such as steroids, flavones, alkaloids, carbohydrates, glycosides, saponins, tannins, terpenoids and coumarin. Eight different polyphenols (five phenolic acids, vanillic, benzoic, p-coumaric, gallic and syringic acid, and three types of flavonoids, naringenin, catechin and kaempferol) were reported from Ashwagandha. Each part of this plant holds an assortment of different metabolites, and the metabolite concentrations vary among the different chemotypes. Ashwagandha has been used for a variety of ailment since a long time by traditional medicinal systems. It has been used for a range of diseases such as diabetes, emaciation, arthritis and rheumatoid arthritis-related inflammations, some kinds of seizures, diarrhoea, dermatitis and insect bite and specially used in the treatment of nervous disorder. The importance of Ashwagandha in medicinal treatments has attracted the attention of a large number of scientists; as a result, numerous experiments have been carried out, which have verified the therapeutic properties of Ashwagandha. Further, the efforts are being taken for the breeding strategies via conventional breeding as well as plant tissue culture techniques and gene transformation for the improvement of withanolide contents. This chapter gives an extensive insight on the various aspects such as basic introduction, classification, botanical description, bioactive molecules, medicinal properties and commercially available products. Furthermore, this chapter narrates the several breeding approaches for the improvement of withanolide contents of Ashwagandha.
Drug development from medicinal plant genomic res.
Context: Withania (Solanaceae) species are known to be a rich source of withanolides, which have shown several biological properties.
Objective: To identify the compounds responsible for Withania adpressa Coss. antioxidant activity and further test them for their NF-κB inhibition and antiproliferative activity in multiple myeloma cells.
Materials and methods: Compounds were obtained from the EtOAc extract of W. adpressa leaves. Structure elucidation was carried out mainly by 1D- and 2D-NMR, and mass spectrometry. Isolated compounds were tested in a dose-response for their in vitro NF-κB inhibition and antiproliferative activity in multiple myeloma cells after 5 and 72 h treatment, respectively.
Results: The fractionation resulted in the isolation of a new glycowithanolide named wadpressine (5) together with withanolide F, withaferin A, coagulin L, and nicotiflorin. The latter showed a moderate ability to scavenge free radicals in DPPH (IC50 = 35.3 µM) and NO (IC50 = 41.3 µM) assays. Withanolide F and withaferin A exhibited low µM antiproliferative activity against both multiple myeloma cancer stem cells and RPMI 8226 cells. Furthermore, they inhibited NF-κB activity with IC50 values of 1.2 and 0.047 µM, respectively. The other compounds showed a moderate inhibition of cell proliferation in RPMI 8226 cells, but were inactive against cancer stem cells and did not inhibit NF-κB activity.
Discussion and conclusions: One new glycowithanolide and four known compounds were isolated. Biological evaluation data gave further insight on the antitumor potential of withanolides for refractory cancers.
Epidemiological studies consistently indicate that consumption of fruits and vegetables lowers cancer risk in humans and suggest that certain dietary constituents may be effective in preventing colon cancer. Plant-derived phenolic compounds manifest many beneficial effects and can potentially inhibit several stages of carcinogenesis in vivo. In this study, we investigated the efficacy of several plant-derived phenolics, including caffeic acid phenethyl ester (CAPE), curcumin, quercetin and rutin, for the prevention of tumors in C57BL/6J-Min/+ (Min/+) mice. These animals bear a germline mutation in the Apc gene and spontaneously develop numerous intestinal adenomas by 15 weeks of age. At a dietary level of 0.15%, CAPE decreased tumor formation in Min/+ mice by 63%. Curcumin induced a similar tumor inhibition. Quercetin and rutin, however, both failed to alter tumor formation at dietary levels of 2%. Examination of intestinal tissue from the treated animals showed that tumor prevention by CAPE and curcumin was associated with increased enterocyte apoptosis and proliferation. CAPE and curcumin also decreased expression of the oncoprotein beta-catenin in the enterocytes of the Min/+ mouse, an observation previously associated with an antitumor effect. These data place the plant phenolics CAPE and curcumin among a growing list of anti-inflammatory agents that suppress Apc-associated intestinal carcinogenesis.
Recent epidemiological studies suggest that non-steroidal anti-inflammatory drugs (NSAIDs) reduce the risk of several cancers including breast cancer. This meta-analysis examined the studies on NSAID use and breast cancer. The estimators of relative risk and associated variances, which have been adjusted for the greatest number of confounders, were abstracted and included in the meta-analysis. Combined estimators of relative risk (RR) were calculated using either fixed or random effect models. Meta-analyses were performed on 6 cohort studies (number of cases ranged from 14 to 2414) and 8 case-control studies (number of cases ranged from 252 to 5882). The combined estimate of relative risk was 0.82 (95% confidence interval [CI] = 0.75-0.89). The combined estimate for cohort studies was 0.78 (95% CI = 0.62-0.99) and was 0.87 (95% CI = 0.84-0.91) for case-control studies. The findings of this meta-analysis suggest that NSAID use may be associated with a small decrease in the risk of breast cancer. However, the available data are insufficient to estimate the dose-response effect for duration and frequency of use of any particular types of NSAID.
From the leaves of Withania somnifera ( Solanaceac ), collected from Tamil Nadu, a new withanolide, 3αmethoxy-2,3-dihydro-27-deoxywithaferin A (1) in addition to the known derivatives withaferin A (4), 2,3-dihydrowithaferin A (5) 3β-methoxy-2,3-dihydrowithaferin A (2) and 27-deoxywithaferin A (3) have been isolated, and their structures elucidated on the basis of physical, chemical and spectral methods.
Tissue cultures were derived from seeds of Corchorus olitorius, C. capsularis, Dioscorea deltoidea, Withania somnifera, Rivea nervosa, and Yucca glauca. The fatty-acid composition of the lipids from these cultures, as well as from the seeds of Y. glauca, C. capsularis, and C. olitorius, was determined by glc. In most tissue cultures, the predominant fatty acids were C16:0 and C18:1. In each case the seeds contained C18:2 as the predominant fatty acid, suggesting that the tissue cultures had at least, in part, lost their ability to elongate and desaturate fatty acids.
Three new withanolides, physagulins E (1), F (2) and G (3) were isolated from the fresh berries of Physalis angulata L. (Solanaceae). Their structures were established as (20S,22R)-15α-acetoxy-5α,6β,14α,28-tetrahydroxy-1-oxowitha-2,16,24 -trienolide-28-O-D-glucopyranoside (1), (20R,22R)-15α-acetoxy-16β,17β-epoxy-5α,6β-14β-trihydroxy-1-oxo-w itha-2,24-dienolide (2) and (20R,22R)-15α-acetoxy-16β,17β-epoxy-5α,6β,14β,28-tetrahydroxy-1- oxo-witha-2,24-dienolide 28-O-β-D-glucopyranoside (3) by spectroscopic means.
Three new withanolides, physagulins A (1), B (2) and D (3), were obtained from the methanolic extract of the fresh leaves and stems of Physalis angulata L. (Solanaceae). Their structures were established as (20S, 22R)-15α-acetoxy-5β, 6β-epoxy-14α-hydroxy-1-oxowitha-2, 16, 24-trienolide (1), (20S, 22R)-15α-acetoxy-5α-chloro-6β, 14α-dihydroxy-1-oxowitha-2, 16, 24-trienolide (2) and (20S, 22R)-1α, 3β, 27-trihydroxywitha-5, 24-dienolide 3-O-β-D-gluco-pyranoside (3) by spectroscopic means.
The preparations of cyclopropanone (1), methylcyclopropanone (2), 2,2-dimethylcyclopropane (3) and tetramethylcyclopropane (4), are described. The spectral properties of these molecules demonstrate unambiguously the ring closed structure for cyclopropanones. The reactions of cyclopropanones with methanol, diazomethane and furan are employed as chemical means of characterization.
This chapter focuses on withanolides that mainly occur in the Solanaceous plants. The withanolides are a group of naturally occurring steroids built on an ergostane skeleton, in which C-22 and C-26 are appropriately oxidized to form a δ-lactone ring. Withanolides generally contain 28 carbon atoms with polyoxygenated functionalities. A common feature of all known withanolides, including the related modified ergostane derivatives, is oxidation at C-1, C-22, and C-26. Over 90% of withanolides contain a 1-oxo-group. C-26 is oxidized in most instances to the carboxylic acid level, thus, allowing the formation of a 26, 22 lactone. Hydroxylation is a common feature in withanolides. Withanolide glycosides isolated so far are listed with their physical constants in the chapter. Mass spectrometry is a useful tool in diagnosing the characteristics of a withanolide. The molecular ion in electron impact is either weakly present or totally absent in some cases. Also, there are several investigations on the microbiological transformations of withanolides.
Two new withanolides, sominone (1α, 3β, 27-trihydroxy-22 (R)-witha-5,24-dienolide) (1) and sominolide (4β,27-dihydroxy- 14α,15α-epoxy-1-oxo-22- (R)-witha-2, 24-dienolide) (2) were isolated from the herbs of Withania somnifera Dun. (Solanaceae). The elucidation of their structures is based on extensive spectroscopic studies.
An ethyl acetate-soluble extract of the leaves and stems of Physalis philadelphica has been investigated, leading to the isolation of three new withanolides, philadelphicalactones A (1) and B (2), and ixocarpalactone B (3), four known withanolides, ixocarpalactone A (4), withaphysacarpin (5), 18-hydroxywithanolide D (6), and withanone (7), one new ceramide, (2S,3S,4R,9E)-1,3,4-trihydroxy-2-[(2′R)-2′-hydroxytetracosanoylamino]-9-octadecene (8), two known ceramides, (2S,3S,4R)-2-[(2′R)-2′-hydroxytetracosanoylamino]-1,3,4-octadecanetriol (9), and (2S,3S,4R)-2-tetracosanoylamino-1,3,4-octadecanetriol (10), as well as the known chlorophyllide a (11). The structures of the new compounds were elucidated based on spectroscopic and chemical methods. Single-crystal X-ray diffraction analysis was used to confirm the relative stereochemistry of compounds 1 and 4. The absolute stereochemistry of compounds 1–4 and 8 was established by Mosher ester methodology and chemical transformation. All isolates were evaluated for their potential cancer chemopreventive properties utilizing in vitro assays to determine quinone reductase induction and inhibition of murine epidermal JB6 cell transformation.
Three new withanolides (C28 steroids possessing a 6-membered ring lactone in the side chain) have been isolated from Withania somnifera (Solanaceae) growing in South Africa and characterized as 4β-hydroxy-1-oxo-5β,6β-epoxywitha-2,24-dienolide (IIIa), 4β,20α,(R)dihydroxy-1-oxo-5β,6β-epoxywith-2-enolide (IVa), and 4β-hydroxy-1-oxo-5β,6β-epoxywith-2-enolide (Va). The major steroidal components of the above plant are the known withaferin A (4β,27-dihydroxy-1-oxo-5β,6β-epoxywitha-2,24-dienolide) and withanolide D (4β,20α,(R)-dihydroxy-1-oxo-5β,6β-epoxywitha-2,24-dienolide). The structures assigned to compounds IIIa, IVa and Va are based on spectral evidence (NMR, IR and UV), analysis of their fragmentation under electron impact, as well as on chemical degradation to known compounds.
The fruits of Physalis philadelphica, known commonly as tomatillos, are an ingredient of the condiment ''salsa verde''. As part of an ongoing project to discover natural product cancer chemopreventive agents, an ethyl acetate-soluble extract of the commercially available fresh fruits of P. philadelphica was found to induce quinone reductase activity in cultured Hepa 1c1c7 murine hepatoma cells. Bioassay-directed fractionation of an EtOAc extract of the fruits, aided by LC/MS, led to the isolation of a series of structurally related withanolides. One novel substance, 2,3-dihydro-3-methoxywithaphysacarpin (1), and two known compounds, withaphysacarpin (2) and 24,25-dihydrowithanolide D (3), were isolated, with the structure of 1 characterized spectroscopically. All three withanolides significantly induced quinone reductase activity in Hepa 1c1c7, TAPclBP(r)c1, and BP(r)cl murine hepatoma cells, suggesting that these compounds are monofunctional inducers, specifically elevating phase II enzymes responsible for detoxification, while not influencing phase I enzymes that may activate carcinogens.
Study of antitumor and radiosensitizing properties of W. somnifera (Ashwagandha), a well known medicinal plant, have yielded encouraging results. The alcoholic extract of the dried roots of the plant as well as the active component withaferin A isolated from the extract showed significant antitumor and radiosensitizing effects in experimental tumors in vivo, without any noticeable systemic toxicity. Withaferin A gave a sensitizer enhancement ratio of 1.5 for in vitro cell killing of V79 Chinese hamster cells at a non toxic concentration of approximately 2 microM. The mechanism of action of this compound is not known. The studies so far indicate that W. somnifera could prove to be a good natural source of a potent and relatively safe radiosensitizer/chemotherapeutic agent. Further studies are needed to explore the clinical potential of this plant for cancer therapy.
The anthocyanins (1-3) and cyanidin isolated from tart cherries exhibited in vitro antioxidant and antiinflammatory activities comparable to commercial products. The inhibition of lipid peroxidation of anthocyanins 1-3 and their aglycon, cyanidin, were 39, 70, 75, and 57%, respectively, at 2-mM concentrations. The antioxidant activities of 1-3 and cyanidin were comparable to the antioxidant activities of tert-butylhydroquinone and butylated hydroxytoluene and superior to vitamin E at 2-mM concentrations. In the antiinflammatory assay, cyanidin gave IC50 values of 90 and 60 mM, respectively, for prostaglandin H endoperoxide synthase-1 and prostaglandin H endoperoxide synthase-2 enzymes.
The inhibitory action of tea (Camellia sinensis) and tea components against cancer formation has been demonstrated in different animal models involving different organ sites in many laboratories. The possible preventive activity of tea against cancer in humans, however, is not clear. A critical question is whether the information obtained from animal studies is applicable to humans because of possible species differences or the difference in the quantity of tea used in animal studies and that consumed by humans. This article will discuss the results from animal studies and possible cancer inhibitory mechanisms that might be applicable to human cancer prevention. To provide a basis for more quantitative analyses of the effect of tea on carcinogenesis, the levels of tea polyphenols in blood, urine and tissue samples have been analyzed, and the pharmacokinetic properties of tea polyphenols studied. Studies with cell lines have demonstrated that tea polyphenols affect signal transduction pathways, inhibit cell proliferation and induce apoptosis, but the effective concentrations are usually much higher than those observed in blood and tissues. More mechanistic studies in these areas will help us to understand the inhibitory action of tea against carcinogenesis and provide background for evaluating the effects of tea consumption on human carcinogenesis.
The prostaglandin endoperoxide H synthases-1 and 2 (PGHS-1 and PGHS-2; also cyclooxygenases-1 and 2, COX-1 and COX-2) catalyze the committed step in prostaglandin synthesis. PGHS-1 and 2 are of particular interest because they are the major targets of nonsteroidal anti-inflammatory drugs (NSAIDs) including aspirin, ibuprofen, and the new COX-2 inhibitors. Inhibition of the PGHSs with NSAIDs acutely reduces inflammation, pain, and fever, and long-term use of these drugs reduces fatal thrombotic events, as well as the development of colon cancer and Alzheimer's disease. In this review, we examine how the structures of these enzymes relate mechanistically to cyclooxygenase and peroxidase catalysis, and how differences in the structure of PGHS-2 confer on this isozyme differential sensitivity to COX-2 inhibitors. We further examine the evidence for independent signaling by PGHS-1 and PGHS-2, and the complex mechanisms for regulation of PGHS-2 gene expression.
Curcumin I, curcumin II (monodemethoxycurcumin) and curcumin III (bisdemethoxycurcumin) from Curcuma longa were assayed for their cytotoxicity, antioxidant and anti-inflammatory activities. These compounds showed activity against leukemia, colon, CNS, melanoma, renal, and breast cancer cell lines. The inhibition of liposome peroxidation by curcumins I-III at 100 microg/ml were 58, 40 and 22%, respectively. The inhibition of COX-I and COX-II enzymes by the curcumins was observed. Curcumins I-III were active against COX-I enzyme at 125 microg/ml and showed 32, 38.5 and 39.2% inhibition of the enzyme, respectively. Curcumins I-III also showed good inhibition of the COX-II enzyme at 125 mg/ml with 89.7, 82.5 and 58.9% inhibition of the enzyme, respectively.
Nonsteroidal anti-inflammatory drugs may reduce the incidence of intestinal carcinoma, presumably through inhibition of cyclooxygenase-2 (COX-2). The authors correlated tumor expression of COX-2 with clinicopathologic features in tissues from patients with gastric carcinoma.
Thirty-three surgical specimens, including carcinomas and corresponding noncancerous mucosa, were sampled. Reverse transcription-polymerase chain reaction analysis was performed concomitantly for COX-1 and COX-2. A COX-2 index was determined from the band density ratio of COX-2 to constitutively expressed COX-1. Immunohistochemical staining with COX-2 antibody and routine histologic assessment were performed in the same specimens.
The COX-2 index in gastric carcinoma was significantly higher than in normal mucosa (3.4 +/- 0.7 vs. 2.2 +/- 0.7; P < 0.05). COX-2 indices were significantly higher in gastric carcinoma tissues with deep invasion; indices for pT1, pT2, pT3, and pT4 carcinomas were 0.8 +/- 0.3, 2.8 +/- 0.5, 4.3 +/- 1.0, and 8.8 +/- 5.5, respectively (P < 0.05). Immunohistochemistry demonstrated COX-2 protein diffusely in the cytoplasm of tumor cells but not in surrounding stroma or in noncancerous mucosa.
COX-2 mRNA expression in gastric carcinoma tissue is correlated closely with depth of invasion, indicating that COX-2 is involved in the growth of gastric carcinoma.
Seven new withanolide glycosides called withanosides I, II, III, IV, V, VI, and VII were isolated from an Indian natural medicine, Ashwagandha, the roots of Indian Withania somnifera DUNAL. (Solanaceae), together with four known compounds, withaferin A, 5 alpha,20 alpha(F)(R)-dihydroxy-6 alpha,7 alpha-epoxy-1-oxowitha-2,24-dienolide, physagulin D, and coagulin Q. The structures of withanosides I, II, III, IV, V, VI, and VII were determined based on chemical and physicochemical evidence. Principal constituents, withanoside VI (10 and 30 microM) and withaferin A (10 microM), attenuated the tachyphylaxis to clonidine on electrically stimulated guinea-pig ileum in vitro.
Milled Piper methysticum roots were extracted sequentially with hot water and methanol. Cyclooxygenase (COX) enzyme inhibitory assay directed purification of the methanol extract yielded bornyl esters of 3,4-methylenedioxy cinnamic acid (1) and cinnamic acid (2), pinostrobin (3), flavokawain B (4), and 5,7-dimethoxyflavanone (5). The structures of compounds 1-5 were accomplished by spectral experiments. The aqueous extract contained previously reported kava lactones, as confirmed by TLC analysis. Compounds 3 and 5 were isolated for the first time from kava kava roots. Compound 4 showed the highest COX-I inhibitory activity at 100 microg/mL. All the compounds tested gave good COX-I and moderate COX-II enzyme inhibitory activities at 100 microg/mL. This is the first report of COX-I and -II inhibitory activities for compounds 1-5.
In this study the role of cyclooxygenase-2 (COX-2) in primitive neuroectodermal tumor (PNET) the most malignant brain tumors of childhood was investigated. COX-2 expression in human brain tumor biopsy samples (seven/seven) was about 6-8-fold higher than normal brain tissue and several PNET cell lines also express COX-2. The effect of selective COX-2 inhibitors, celecoxib and rofecoxib on the growth of two PNET cell lines (DAOY and PFSK) was determined. Celecoxib was more potent than rofecoxib in suppressing cell growth. Growth inhibition by celecoxib and rofecoxib was independent of Bcl-2 expression. Celecoxib suppressed the expression of Akt and activated the caspase-3 in DAOY and PFSK, whereas rofecoxib did not have such an effect.
Limonoids have been shown to inhibit the growth of estrogen receptor-negative and -positive human breast cancer cells in culture. The primary objective of this study was to test the antiproliferative activity of limonoids (obacunone 17 beta-D-glucopyranoside, nomilinic acid 17 beta-D-glucopyranoside, limonin, nomilin, and a limonoid glucoside mixture), found in high concentrations in mandarin (Citrus reticulata Blanco), against a series of human cancer cell lines. The human cancer cell lines included leukemia (HL-60), ovary (SKOV-3), cervix (HeLa), stomach (NCI-SNU-1), liver (Hep G2), and breast (MCF-7). The growth-inhibitory effects of the four limonoids and the limonoid glucoside mixture against MCF-7 cells were significant, and the antiproliferative activity of the different citrus limonoids was also dose and time dependent. No significant effects were observed on growth of the other cancer cell lines treated with the four individual limonoids at 100 micrograms/ml. At 100 micrograms/ml, the limonoid glucoside mixture demonstrated a partial inhibitory effect on SKOV-3 cancer cells. With use of flow cytometry, it was found that all the limonoid samples could induce apoptosis in MCF-7 cells at relatively high concentrations (100 micrograms/ml). Considering the high concentration needed to induce apoptosis, it is unlikely that this is the primary mechanism of action for the cytotoxic effects seen with limonoids in this study. Further work is needed in this area to establish the mechanism of action of citrus limonoids on human breast cancer cells.
Thirty-seven naturally occurring withanolides (1-37), previously isolated in our laboratories, were evaluated for their potential to induce quinone reductase with cultured murine hepatoma cells (Hepa 1c1c7). Spiranoid (29, 32) and 18-functionalized withanolides (2-5, 7-9, 24) were found to be potent inducers of the enzyme, while 5alpha-substituted derivatives exhibited weak activity. Preliminary studies were performed with compound 29 to evaluate enzyme-inducing capacity in multiple organ sites of BALB/c mice. Significant induction was observed in liver and colon, but not in lung, stomach, or mammary gland.
The chemopreventive effect of Withania somnifera hydroalcoholic root extract (WSRE) on 7,12-dimethylbenz[a]anthracene (DMBA)-induced skin cancer was investigated in Swiss albino mice. The skin lesions were induced by the twice-weekly topical application of DMBA (100 nmol/ 100 microliters acetone) for 8 wk on the shaved back of mice. WSRE was administered at the maximal tolerated dose of 400 mg/kg p.o. three times per week on alternate days 1 wk before DMBA and continued for 24 wk thereafter. The results of the study revealed a significant decrease in incidence and average number of skin lesions in mice compared with DMBA alone at the end of Week 24. Biochemical parameters were assessed in the lesions of WSRE-treated and untreated control mice. A significant impairment was noticed in the levels of reduced glutathione, malondialdehyde, superoxide dismutase, catalase, glutathione peroxidase, and glutathione S-transferase in skin lesions of DMBA-treated control mice compared with vehicle-treated mice. These parameters were returned to near normal by administration of WSRE to DMBA-treated mice. The above findings were supported by histopathological studies. From the present study, it can be inferred that WRSE possesses potential chemopreventive activity in this experimental model of cancer. The chemopreventive activity may be linked to the antioxidant/free radical-scavenging constituents of the extract. The anti-inflammatory and immunomodulatory properties of WSRE are also likely to contribute to its chemopreventive action.
Bioassay-guided purification of an extract of Cucurbita andreana fruits yielded cucurbitacins B (1), D (2), E (3), and I (4). These cucurbitacins were evaluated for their inhibitory effects on the growth of human colon (HCT-116), breast (MCF-7), lung (NCI-H460), and central nervous system (CNS) (SF-268) cancer cell lines, cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) enzymes and on lipid peroxidation. Inhibitory activities of cucurbitacins B (1), D (2), E (3) and I (4), respectively, were for colon 81.5, 80.4, 77, and 65% at 0.4 microM, breast 87, 78, 66.5, and 12% at 0.4 microM, lung 96, 43, 37 and 2% at 0.1 microM and CNS 92, 25, 24 and 4% at 0.05 microM. Adriamycin (doxorubicin) was used as a positive control, which showed 64, 47, 45 and 71% inhibition of HCT-116 (colon), MCF-7 (breast), NCI-H460 (lung) and SF-268 (CNS) cell lines, respectively, at 0.3 x 10(-5) M. Compounds 1, 2, 3, and 4 inhibited the COX-2 enzyme by 32, 29, 35, and 27%, respectively, at 100 microg/ml. However these compounds did not inhibit the COX-1 enzyme at this concentration. Ibuprofen, naproxen and vioxx, commercial antiinflammatory drugs, were tested as controls for the inhibition of COX-1 and COX-2 enzymes at concentrations of 2.1, 2.5 and 1.67 microg/ml, respectively. Ibuprofen and naproxen exhibited 59 and 95% COX-1, and 53 and 79% COX-2 inhibitory activities, respectively. Vioxx showed specific COX-2 inhibition by 71%. Also, cucurbitacins 1 and 4 inhibited lipid peroxidation by 59 and 23%, respectively, at 100 microg/ml.
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