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Inhibitory effect of andrographolide from Andrographis paniculata on PAF-induced platelet aggregation
Abstract
Andrographolide, an active principle of the Chinese drug Andrographis paniculata, used for prevention and treatment of common cold in Scandinavia and known as an antiinflammatory, antiviral, antithrombotic, hypotensive and antiatherosclerotic drug, was investigated for its suggested influence on the biosynthesis of eicosanoids and the platelet-activating factor (PAF). Whereas in isolated human polymorph-nuclear leukocytes (PMNL) no influence on the biosynthesis was found, it could be shown that andrographolide inhibits PAF-induced human blood platelet aggregation in a dose dependent manner (IC50-5 microM). These results indicate that andrographolide has a mechanism of action different from that of non-steroidal antiinflammatory drugs (NSAID) and most likely associated with the cardiovascular and antithrombotic activity described of Andrographis paniculata.
... Andrographolide is one of the major active compounds of A. paniculata., playing an important role in the inflammatory process and cyclooxygenase (COX) enzyme expression [4,5]. Moreover, some in vitro studies have shown that andrographolide inhibited platelet-activating-factor (PAF) induced platelet aggregation in humans [6] and thrombin-induced platelet aggregation in rats [7]. Platelets are essential for primary hemostasis, and they also have an important proinflammatory role. ...
... A pharmacokinetic study after the oral administration of 60 mg of andrographolide revealed that a maximum plasma level of approximately 1.9 M was achieved at 1.5-2 hours [9]. This level has been found to be enough to reveal some anti-PAF effects [6,9]. To study the platelet aggregation, blood was therefore taken in the morning of the day of AP administration before the AP was dispensed (i.e., 0 hours) and then 2 and 24 hours after its administration. ...
... One of its major biological extract compounds, andrographolide, possibly contributes to those pharmacological actions. Andrographolide also possesses antiplatelet activity [6,7,15]. It inhibited PAF-induced human blood platelet aggregation [6] and thrombin-induced washed rat platelet aggregation [7] in the in vitro studies of [15]. ...
Background. Andrographis paniculata (AP) has been used in Thai traditional medicine to treat various infections, including the common cold and fever. Its bioactive compound, andrographolide, has shown antiplatelet activities in an in vitro study model. Since clinical studies of the effects of AP on the human platelet function have never been reported, we investigated its effect on platelet activity in ten healthy volunteers. Methods . Two grams of AP was taken 3 times within one day. The blood was withdrawn by venipuncture before and 2 and 24 hours after the AP administration to analyze the effects of AP on platelet aggregation, the expression of enzyme cyclooxygenase (COX) mRNA and protein, and TXB 2 , including P-selectin. Result . Even though there was no significant change in the studied parameters, this study exhibited patient-to-patient variability in platelet function. It was found that ADP-induced platelet aggregation tended to decrease after AP administration, while epinephrine-induced platelet aggregation in females tended to be higher than that in males for the entire study period. Moreover, COX-1 mRNA levels tended to decrease while P-selectin levels tended to rise after AP administration. Conclusion . These controversial results are possibly due to the multifactorial mechanisms of platelet aggregation as well as the multichemical composition of AP. Further study, probably at the molecular level, is needed to unveil the underlying mechanisms of action of AP.
... Ex Nees (Family: Acanthaceae) (Chakravarti and Chakravarti, 1951;Islam, 2016). AGL mainly used for the prevention and treatment of common cold in many countries and known as an anti-inflammatory, antiviral, antithrombotic, hypotensive, and antiatheroscelerotic drug (Amroyan et al., 1999). ...
... Moreover, AGL (IC 50 5 µM) was found to inhibit plateletactivating factor (PAF)-induced human blood platelet aggregation in a dose dependent manner (Amroyan et al., 1999). In a previous study, Zhang and Tan (1997) suggested that, the crude water extract of A. paniculata, its three semi-purified ethyl acetate, n-butanol and aqueous fractions, as well as AGL significantly reduced mean arterial blood pressure (MAP) in anesthetized Sprague-Dawley rats between ED 50 values of 5.0 to 11.4 mg/kg. ...
... Toxins like fragments of destroying bacteria induce the synthesis of PAF, causing a reduction in blood pressure and reduces volume of blood pumped by the heart, thus leading to shock and even death. AGL inhibition PAF in rats (Zhang and Tan, 1997) and in human (Amroyan et al., 1999) is a good indication for its anti-hypotentive and related other events. ...
Recently, the use of plant-derived medicines is increasing interest in the prevention and treatment of a variety of disorders including metabolic syndromes. Metabolic syndrome is one of the major risk factors for cardiovascular diseases (CVDs) and incidence of mortality worldwide. Scientific evidence suggests that Andrographis paniculata and its derived components, especially andrographolide (AGL) and its analogs/derivatives have a broad spectrum of biological activities. This review aims to sketch the activity of AGL and its analogs/derivatives against the components of metabolic syndromes such as diabetes, hyperlipidemia, hypertension, and obesity. Additionally, AGL activity against CVDs is also summarized. The finding suggests that AGL and its analogs/derivatives have a potential role in the management of metabolic syndrome; however, more studies should be conducted to evaluate their effectiveness.
... mg/mL) had no remarkable effects on thrombin induced platelet aggravation. Moreover, Arnroyan et al. [152] found AG (0.35, 3.50 and 35.00 mg/mL) inhibited PAF-induced human platelet aggregation, with equal efficiency to PAFantagonists Ginkgo extract (Ginkgo hi/aha) containing Ginkgolides. However, the underlying mechanism of AG was different from that of non-steroidal anti-inflammatory drugs (NSAID), which was mainly evidenced by the fact that AG made no differences to the calcium ionophore and AA-induced biosynthesis of any 5-, 12-and 15-lipoxygenase pathway products, such as LTB4, 6E-LTB4, 5(S) 6E-LTB4, 5-HETE, 12-HETE and 15-HET, and 12-HHT (the cyclooxygenase product). ...
... In the cellular model of AS (ECs, platelets, monocyte/macrophage-like cells, and VSMCs), the concentration range of AG was 0.35e35.00 mg/mL [129,140,147,152,158,164]. In the cellular models of ASCVD, the concentration of AG was 1.75e3.50 ...
Atherosclerotic cardiovascular disease (ASCVD) frequently results in sudden death and poses a serious threat to public health worldwide. The drugs approved for the prevention and treatment of ASCVD are usually used in combination but are inefficient owing to their side effects and single therapeutic targets. Therefore, the use of natural products in developing drugs for the prevention and treatment of ASCVD has received great scholarly attention. Andrographolide (AG) is a diterpenoid lactone compound extracted from Andrographis paniculata. In addition to its use in conditions such as sore throat, AG can be used to prevent and treat ASCVD. It is different from drugs that are commonly used in the prevention and treatment of ASCVD and can not only treat obesity, diabetes, hyperlipidaemia and ASCVD but also inhibit the pathological process of atherosclerosis (AS) including lipid accumulation, inflammation, oxidative stress and cellular abnormalities by regulating various targets and pathways. However, the pharmacological mechanisms of AG underlying the prevention and treatment of ASCVD have not been corroborated, which may hinder its clinical development and application. Therefore, this review summarizes the physiological and pathological mechanisms underlying the development of ASCVD and the in vivo and in vitro pharmacological effects of AG on the relative risk factors of AS and ASCVD. The findings support the use of the old pharmacological compound (‘old bottle’) as a novel drug (‘novel wine’) for the prevention and treatment of ASCVD. Additionally, this review summarizes studies on the availability as well as pharmaceutical and pharmacokinetic properties of AG, aiming to provide more information regarding the clinical application and further research and development of AG.
... The entire plant and Andrographolide have shown various pharmacological activities such as stable pumping heart and good circulation of blood (4), agent for the treatment of fever, cold, laryngitis, diarrhea, inflammatory diseases, respiratory infections, and a variety of other chronic and infectious diseases (5). anti-inflammatory (6), antipyretic (7), immunostimulant (8), antiviral (9), anti-bacterial (10), hepatoprotective (11), anti-fertility (12), anti-thrombotic (13), anti-diabetic (14), anti-cancer (15), and anti-oxidant (16). Study reported that Andrographis paniculata is a immunoprotective ayurvedic herb against respiratory viral infections (17). ...
... . The entire plant and Andrographolide have shown various pharmacological activities such as stable pumping heart and good circulation of blood (4), agent for the treatment of fever, cold, laryngitis, diarrhea, inflammatory diseases, respiratory infections, and a variety of other chronic and infectious diseases(5). anti-inflammatory (6), antipyretic(7), immunostimulant (8), antiviral(9), anti-bacterial (10), hepatoprotective (11), anti-fertility (12), anti-thrombotic(13), anti-diabetic(14), anti-cancer(15), and anti-oxidant (16). Study reported that Andrographis paniculata is a immunoprotective ayurvedic herb against respiratory viral infections(17). ...
Andrographis paniculata (family Acanthaceae) is known as Kalmegh, one of the traditionally used important medicinal plant contains several biologically active phytochemical including andrographolide. A. paniculata is broadly used by healthcare practitioners in India and also used in different traditional medicinal system. In this study, the leaves of A. paniculata were collected from West Medinipur, East Medinipur, South 24 Parganas, Purulia and Hooghly district of West Bengal, India. This study aiming towards validation and development of a simple, precise and reproducible reverse-phase high-performance liquid chromatography (RP-HPLC) and high-performance thin layer chromatography (HPTLC) methods for quantification of andrographolide in A. paniculata extracts. The validated RP-HPLC and HPTLC study confirmed that different concentrations of andrographolide content present in the plant samples, which are collected from above different districts of West Bengal, India. The amounts of andrographolide were found to be 2.71% (w/w), 3.19% (w/w), 1.83% (w/w), 1.73% (w/w) and 2.94% (w/w) in RP-HPLC study and 2.13% (w/w), 2.51% (w/w), 1.01% (w/w), 1.25% (w/w) and 2.15% (w/w) in HPTLC study. This precise, reproducible, accurate and specific method can be used for the quantification of andrographolide in kalmegh, as per the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) guidelines recommendations.
... One study found that two diterpene lactones, including andrographolide, extracted from AP may inhibit thrombin-induced platelet aggregation (Thisoda et al. 2006). In another study, andrographolide and AP inhibited platelet-activating factor (PAF)-induced human blood platelet aggregation (Amroyan et al. 1999). Although, in recent years, AP has been reported to inhibit platelet aggregation potentially, it has not been observed to affect the mRNA expression of COX or the production of TXB 2 and P-selectin in clinical study (Sirikarin et al. 2018). ...
... In the present study, we first found that DAS significantly inhibited TXA 2 production but had no effect on 6-keto-PGF 1a production, which may be related to the specific inhibition of thromboxane synthesis by DAS. These results support previous research suggesting that the mechanism of action of andrographolide and other diterpenoid lactones differs from that of NSAIDs (Amroyan et al. 1999). As a classic antiplatelet aggregation and nonsteroidal anti-inflammatory drug, aspirin significantly reduces the contents of TXA 2 and PGI 2 by inhibiting COX activity and platelet aggregation. ...
Context
Dehydroandrographolide succinate (DAS) is mainly used in the clinical treatment of various infectious diseases. Its potential effects on platelet aggregation and blood coagulation systems have not been reported systematically.
Objective
To explore whether DAS exerts an antithrombotic effect and its internal mechanism.
Materials and methods
Human blood samples and Sprague-Dawley (SD) rats divided into control, aspirin (30 mg/kg), and DAS groups (200, 400 and 600 mg/kg) were used to measure the platelet aggregation rate, coagulation function, coagulation factor activity, and contents of thromboxane B2 (TXB2) and 6-keto-prostaglandin F1α (6-keto-PGF1α). The histopathology of the SD rat gastric mucosa was also observed. All rats were administered intragastric or intraperitoneal injections once a day for 3 consecutive days.
Results
Compared to control group, DAS significantly inhibited the platelet aggregation rate (ED50 = 386.9 mg/kg) by decreasing TXB2 levels (1531.95 ± 649.90 pg/mL to 511.08 ± 411.82 pg/mL) and activating antithrombin III (AT-III) (103.22 ± 16.22% to 146.46 ± 8.96%) (p < 0.05). In addition, DAS significantly enhanced the coagulation factors FV (304.12 ± 79.65% to 443.44 ± 75.04%), FVII (324.19 ± 48.03% to 790.66 ± 225.56%), FVIII (524.79 ± 115.47% to 679.92 ± 143.34%), FX (34.90 ± 7.40% to 102.76 ± 29.41%) and FXI (38.12 ± 10.33% to 65.47 ± 34.08%), increased the content of Fg (2.18 ± 0.39 to 3.61 ± 0.37 g/L), shorten the PT (10.42 ± 0.44 to 9.22 ± 0.21 s), APTT (16.43 ± 1.4 to 14.07 ± 0.75 s) and TT time (37.04 ± 2.13 to 32.68 ± 1.29 s) (p < 0.05), while the aspirin group showed no such effect on these items but showed reduced activity of FII (89.21 ± 21.72% to 61.83 ± 8.95%) and FVIII (524.79 ± 115.47% to 306.60 ± 29.96%) (p < 0.05). Histopathological changes showed aspirin-induced gastric mucosa haemorrhage and the protective effect of DAS in the gastric mucosa.
Conclusions
DAS is more suitable than aspirin in thromboprophylaxis treatment, which provides a reliable theoretical and experimental basis for its clinical application.
... There are many plants having antiinflammatory activity. Some of the plants which have shown antiinflammatory activity, Andrographis paniculata (6), Ocimun sanctum (7), Loasa speciosa (8), Hemigraphis colorata (9), Bergenia ciliate sternb (10), Hyptis suaveolels (11), Hibiscus esculantus (12) and Benincasa hispida (13) were reported. ...
... In Ai and Cg treated rats, it has been shown that the antiinflammatory activity is probably due to decrease in 5-HT and PGE1 (14 & 15). It was also reported, the acute inflammation is due to the releasing of chemical mediators like 5-hydroxy tryptamine (5-HT), histamine, bradykinin and PGE1 in groups treated with Andrographis paniculata (6). Most of the researchers concluded their study by mentioning that the antiinflammatory activity may be due to inhibition of the enzyme cyclooxygenase leading to inhibition of prostaglandin synthesis (16). ...
Introduction and Aim: Inflammation is a symptom associated with many diseases, can be treated with steroidal and non-steroidal anti-inflammatory drugs, which can cause severe side effects when used as long-term treatments. Plants have the ability to synthesize a wide verity of phytochemical compounds as secondary metabolites which shows anti-inflammatory activity. The anti-inflammatory activity of crude extracts of leaves of Jasminum grandiflorum (Jg), Vinca rosea (Vr), Azadirachta indica (Ai), Lawsonia inermis (Li), Nerium indicum (Ni), Calotropis gigantea (Cg), Tectona grandis (Tg), Andrographis paniculata (Ap), Tabernaemontana corymbosa (Tc) and Marsedinia volubilis (Mv) as well as alcoholic extracts of leaves of Cg, Tg and Ap were evaluated in Wistar rats. Methods: Acute anti-inflammatory activity of crude extracts of ten indigenous plants were studied by calculating the volume changes in the hind paw after injecting carrageenan in rats comparing with Ibuprofen which was used as a standard drug in this study. Anti-inflammatory effect of alcoholic extract of leaves of Ap, Tg and Cg (200mg/kg body weight) also studied. Results: The groups treated with crude extract & alcoholic extract of Cg, Tg and Ap showed significant reduction in the oedema compared to control and other plant extracts. The result was very significant in Ap treated rats. Conclusion: Plants are one of the most important sources of medicines. In our study, the anti-inflammatory activity of ten indigenous plants could be due to presence of naturally occurring antioxidant flavonoids. The leaves of Ap are very rich in flavonoids, could be the reason for significant anti-inflammatory activity found in Ap treated rats.
... 3 This combination was tested in controlled clinical trials for the treatment of common cold and influenza-associated uncomplicated upper respiratory infections as well as for the prevention of common colds. [421][422][423][424] The studies confirmed the safety and superior efficacy of this combination regimen as compared with monodrug therapy, 425 presumably because of its antiviral effects, [426][427][428][429][430][431][432] effects on innate and adaptive immunity, [433][434][435][436][437] and anti-inflammatory, antioxidant, and detoxifying effects [438][439][440][441] of both adaptogenic plants as well as due to their synery. 25 It should be noted that the postmarketing pharmacovigilance assessment of Kan Jang showed a high benefit-risk ratio: one adverse event in about 100,000 patients erectile dysfunction, quality of life, improvement of the immune system, and chronic respiratory diseases. ...
... 591,598 As an example, the concentration of andrographolide (the active compound of Andrographis and its combination with Eleutherococcus) in blood plasma of human subjects was approximately 3.5 µM at 2 h after drug uptake, 591 which is adequate for exhibiting an anti-PAF effect in vitro (EC50, 5 µM). 440 A comparison of the results obtained in humans and rats showed that the pharmacokinetics of andrographolide are similar in both species. It was found that andrographolide is rapidly and almost totally absorbed (T1/2abs of about 25 min) into the blood (bioavailability = 91%, F = 0.91) after oral administration of Andrographis extract at a therapeutic dose (20 mg/kg). ...
Adaptogens comprise a category of herbal medicinal and nutritional products promoting adaptability, resilience, and survival of living organisms in stress. The aim of this review was to summarize the growing knowledge about common adaptogenic plants used in various traditional medical systems (TMS) and conventional medicine and to provide a modern rationale for their use in the treatment of stress-induced and aging-related disorders. Adapto-gens have pharmacologically pleiotropic effects on the neuroendocrine-immune system, which explain their traditional use for the treatment of a wide range of conditions. They exhibit a biphasic dose-effect response: at low doses they function as mild stress-mimetics, which activate the adaptive stress-response signaling pathways to cope with severe stress. That is in line with their traditional use for preventing premature aging and to maintain good health and vitality. However, the potential Med Res Rev. 2020;1-74. wileyonlinelibrary.com/journal/med | 1 This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
... Platelet activation and aggregation are two major factors which determine the efficacy of thrombus formation [48]. In previous studies, both andrographolide and A. paniculata were found to suppress platelet aggregation likely through triggering the endothelial nitric oxide synthase (eNOS)-nitric oxide (NO)-cyclic guanylate (cGMP) signaling or inhibiting the Akt-p38 and phospholipase Cγ (PLCγ)-PKC signaling [35,49,50]. Inhibition of thromboxane A 2 (TxA 2 ) and hydroxyl radicals (OH − ) formation may also contribute to the anti-platelet effect of andrographolide in both washed and activated platelets (Fig. 2) [51]. ...
... However, since no Nrf2 induction in andrographolidetreated microglia has been reported, whether the Nrf2 signaling mediates the anti-neuroinflammatory effect of andrographolide remains unknown. In the CNS, the neuroprotective effects of andrographolide may be also mediated by many other mechanisms, such as restoration of BBB integrity [20,21] and synaptic function [27], inhibition of cerebral endothelial cell damage [20,21] and VSMC proliferation [63], promotion of VSMC apoptosis [33] and hippocampal neurogenesis [114], suppression of platelet activation and aggregation [49][50][51], and inhibition of Aβ aggregation [27]. The clinical trial for andrographolide in MS treatment suggests that the andrographolide may have a great potential to be developed as novel clinical drug for CNS disease treatment. ...
Andrographolide is compound extracted from Andrographis paniculata (A. paniculata), a traditional herb that has been used in ancient China and other parts of eastern Asia to treat an array of disorders, such as cancer, rheumatoid arthritis, diarrhea, upper respiratory tract infection, and laryngitis, for a very long history. The mechanisms of action of andrographolide in disease prevention and/or therapy include anti-inflammation, anti-oxidative stress, anti-apoptosis, and/or pro-apoptosis. Pharmacodynamic studies have shown that andrographolide can cross the blood brain barrier and distribute into different brain regions, and therefore its pharmacological effects in the central nervous system (CNS) have begun to be revealed in recent years. For example, andrographolide has been reported to reduce brain infarct volume in several models of cerebral ischemia. In models of Alzheimer's disease (AD), andrographolide not only reduces Aβ aggregation, but suppresses neuroinflammatory response and synaptic dysfunction, which could be evidenced by the reversal of microglia-mediated production of pro-inflammatory cytokines as well as AD-associated decreases in synaptic proteins, such as postsynaptic membrane dense substance-95. Andrographolide may also inhibit the onset and/or progression of Parkinson's disease, multiple sclerosis, and surgery- or diabetes-induced cognitive impairment. Further, andrographolide has been shown to inhibit chronic stress-induced abnormalities in serum corticosterone levels, mood-associated behavior, and hippocampal neurogenesis, suggesting that andrographolide may have a potential to treat psychiatric disorders, such as anxiety and depression. In this review, we summarize and discuss the pharmacological effects of andrographolide in the CNS in hope of revealing more possibilities of andrographolide in disease prevention and/or therapy.
... Interestingly, andrographolide (compound 14), a diterpenoid that was first isolated from Andrographolis paniculata, was also detected in S. cordatum (Islam, 2017). Andrographolide is a versatile compound that has been evaluated for its ability to influence inflammatory, thrombotic, hypertensive and atherosclerotic pathways (Amroyan et al., 1999). The compound has also been evaluated in in vivo assays as a potential drug against T2DM. ...
Type 2 Diabetes Mellitus (T2DM) is a chronic metabolic dysfunction characterized by hyperglycemia. T2DM is a growing global epidemic with diffuse complications, including a high mortality rate. High blood sugar can be lowered by impeding the activities of pancreatic a-amylase and intestinal a-glucosidase enzymes. Although there are a number of orthodox medications used in the management of hyperglycemia, medicinal plants remain a veritable option in many cultures of the world owing to their overall efficacy and affordabil-ity. This study was designed to investigate the hypoglycemic potential of Syzygium cordatum leaf extract fractions in the retardation of pancreatic a-amylase and intestinal a-glucosidase enzymes in vitro. The bioactive components of the active fractions were identified using the Gas Chromatography-Mass Spectrometry (GC-MS) and their potential hypoglycemic properties were assessed using the molecular in silico modelling approach. The in vitro a-amylase and a-glucosidase inhibitory activities of S. cordatum revealed that the organic solvent fractions retarded the digestive enzymes considerably although the standard drug (acarbose) had the least half-maximal inhibitory concentration (IC 50) value. Analytical and computational analysis identified the potential of cubenol, to interact with important residues of a-glucosidase and a-amylase emphasizing its hypoglycemic potential. The result of this study revealed that S. cordatum is a rich source of pharmacologically important bioactive compounds with a remarkable capacity to retard a-amylase and a-glucosidase enzymes. Cubenol was identified as an efficient and safe hypoglycemic agent of S. cordatum.
... It also possesses emmenagogue, emollient, diuretic effects (Murtem & Chaudhry, 2016). It is used to treat upper respiratory infections (influenza, whooping cough, bronchitis and asthma) (Amroyan et al., 1999), snakebites, scorpion sting (Shivashankar et al., 2019), diabetes (Ignacimuthu et al., 2008), dysentery, diarrhoea, cholera) (Poonam & Singh, 2009), disorders of the liver and spleen (Poonam & Singh, 2009), a variety of skin conditions, including warts, eczema, scabies, leprosy, skin allergies, ringworm and skin infections (Suneetha et al., 2011), worm infestations (Ignacimuthu et al., 2008), joint disorders such as rheumatism, frozen and painful joints, gout and other forms of arthritis (Vijayalakshme & Ranganathan, 2011). It is helpful for headaches, cancer, syphilis, HIV/AIDS, piles, drooling, abdominal discomfort, myalgia, renal calculi, Tinea cruris, endogenous toxins, wounds, and piles. ...
Background: Andrographis paniculata (AP) is a plant used in traditional medicines worldwide for its medicinal properties, and for liver disorders. Despite numerous studies on its efficacy, the precise mode of action responsible for its hepatoprotective potential remains unclear. Methods: In this review, traditional uses, bioactive compounds, and pharmacological activity of AP for hep-atoprotection were investigated using ten databases and keywords such as Andrographis paniculata, Hep-atoprotection of AP, and AP in liver disorders and results between 2000 and 2023. Results: The review found that AP has the potential to treat liver disorders, including cancer, and established its anti-inflammatory, antitumor, anti-fibrotic, antiviral potential, and hepatic protection activity through experimental and clinical studies. The review also discussed its safety aspects. Conclusion: AP can potentially treat liver disorders and the findings highlight the need for further research to elucidate the mode of action responsible for AP's hepatoprotective potential and validate its rational use in liver disorders.
... The water extract of A. paniculata was reported to inhibit lipid peroxidation in spontaneously hypertensive rats [12]. Andrographis paniculata was able to inhibit the growth of Staphilococcus aureus, Pseudomonas aeroginosa, Proteus vulgaris, Shigella dysenteriae and Escherichia coli, it was recommended for the treatment of different diseases ranging from bacterial dysentery, gastrointestinal disorders, tonsillitis, pneumonia, pyelonephritis to abscesses [13]. The leaves of Andrographis paniculata Nees, known as ''Fah Talai Joan'' in Thai folklore, are used extensively for the treatment of various diseases such as the bowels and liver, colic, undiagnosed fever, cholagogues and anti-helminthetics etc. Anti-neoplatic constituents from Thai medicinal plants, the methanolic extract from the leaves of A.paniculata Nees. ...
Andrographis paniculata is an herbaceous plant which is commonly known as “King of Bitters” and belongs to the family Acanthaceae. Andrographis paniculata is one of the commonly used herbal medicines worldwide.It is an erect plant which grows mainly as under shrub in tropical moist deciduous forests. It grows erect to a height of 32-100cm in moist shady places with glabrous leaves and white flowers with rose-purple spots on the petals. This plant is the richest source of bioactive constituents. Andrographolide is generally considered an essential bioactive component of plant A. Paniculata. Andrographolide is colorless, crystalline in appearance and has a very bitter taste. the andrographolide are multifarious and include: analgesic, antipyretic, antiretroviral, antimalarial, anti-hyperglycaemic, hepatoprotective, immunemodulatory, protective against alcohol induced toxicity and cardio protective activity and anticancer activity Its phyto extract can protect human against a number of diseases.Kalmegh is used both in Ayurvedic and Unani System of medicines for possess immunological, antibacterial, anti-inflammatory, antithrombotic and hepatoprotective properties. Andrographolide is an interesting pharmacophore with anticancer and immunomodulatory activities and hence has the potential to be developed as an anticancer chemotherapeutic agent as well.. The A. paniculata treats a wide range of diseases in traditional medicinal systems, and its intended benefits must be evaluatedThe present communication deals with the anti-diarrhoeal properties of the alcoholic extract, its fractions and pure compounds isolated from A. paniculata.In the ayurvedic system of medicine currently widely practiced in Indian, Andrographis paniculata is often used in combination with other herbs and health care procedures for helping patients suffering from diverse spectrums of organ pathologies and mental health problems
... The results indicated that the 7 standardized Andrographis paniculata extract may contain other anti-platelet compounds, which contribute to high antiplatelet activity. Amroyan, et al [114] tested andrographolide for PAF-induced platelet aggregation, where, andrographolide inhibited PAF-induced human blood platelet aggregation in a dose dependent manner (IC50 ~5 μM). These results indicated that andrographolide has a mechanism of action different from that of non-steroidal antiinflammatory drugs (NSAID) and most likely associated with the cardiovascular and antithrombotic activity described of Andrographis paniculata. ...
Andrographis paniculata (King of Bitters), also known as Kalmegh, is a member of the Acanthaceae family. Andrographis paniculata is widely cultivated, and its relevance as a medicinal plant is expanding as evidence of its several therapeutic applications grows. Considering the plant's beneficial properties, it might be recommended as a safe and vital medicinal herb for mankind. This herb is rich in chemical components, including lactones, diterpenoids, diterpene glycosides, flavonoids, and flavonoid glycosides. It possesses numerous pharmacological effects, including antibacterial, hepatoprotective, anti-cancer, anticancer, hypoglycemic, immunomodulatory, and hypotensive action. The goal of this study is to conduct a literature review on Andrographis paniculata, specifically papers on therapeutic advantages, chemical features, and pharmacological evaluation. It is widely utilised as a home cure for numerous maladies in the Bangladeshi traditional system of medicine. Steroids, phenols, terpenoids, alkaloids, saponins, and flavonoids were the active chemicals found in Andrographis paniculata. The presence of active components, andrographolide and neo andrographolide
, which are diterpenoids derivatives, contributes to the therapeutic potential of this plant.
... The results indicated that the 7 standardized Andrographis paniculata extract may contain other anti-platelet compounds, which contribute to high antiplatelet activity. Amroyan, et al [114] tested andrographolide for PAF-induced platelet aggregation, where, andrographolide inhibited PAF-induced human blood platelet aggregation in a dose dependent manner (IC50 ~5 μM). These results indicated that andrographolide has a mechanism of action different from that of non-steroidal antiinflammatory drugs (NSAID) and most likely associated with the cardiovascular and antithrombotic activity described of Andrographis paniculata. ...
... Over twenty years prior, a research facility test exhibited that AP hindered development of human bosom malignant growth cells like the medication tamoxifen [25] . Amroyan et al. [26] revealed that andrographolide was successful to stop the amassing of blood platelets that lead to cardiovascular failures and they likewise recommended that andrographolide has a significant impact on initiating the overall protection elements of resistant framework by animating the creation of antibodies just as vague insusceptible reactions, for example, expanded macrophage phagocytosis. An in vitro concentrate with the expanded multiplication of lymphocytes and creation of interleukin-2 (IL-2) affirmed the immunostimulatory action of AP [27] . ...
Andrographis paniculata (Burm.f.) Nees (Acanthaceae) is a medicinal plant traditionally used for the treatment of cold, fever, laryngitis and several infectious diseases ranging from malaria to dysentery and diarrhea in China, India and other south east Asian countries. The plant is claimed to possess immunological, antibacterial, antiinflammatory, antithrombotic and hepatoprotective properties. In Malaysia, the plant is used in folk medicines to treat diabetes and hypertension. The contents of diterpenoids like andrographolide, neo andrographolide and dehydroandrographolide are the chief criteria for monitoring the quality of Andrographis paniculata. Andrographolide, though found in all plant parts, is most concentrated in the leaves. It is a diterpene containing a γ-lactone ring connected to a decalin ring system via an unsaturated C-2 moiety. It has multiple pharmacological properties such as protozoacidal, antihepatotoxic, anti-HIV, anticancer, antitumor, hypoglycemic and hypotensive activities. Andrographolide is an interesting pharmacophore with anticancer and immunomodulatory activities and hence has the potential to be developed as an anticancer chemotherapeutic agent as well. In this review, we have explored the various dimensions of the Andrographis paniculata plant and compiled its vast pharmacological applications to comprehend and synthesize the subject of its potential image of multipurpose medicinal agent. The plant is widely cultivated to large regions of the world and its importance as a medicinal plant is growing up substantially with increasing and stronger reports in support of its multifarious therapeutic uses.
... It's been used in the treatment of fever, upper respiratory infections, acute bacillary dysentery, snake bites, insect bite diabetes, and malaria for a long time [3,4]. Pharmacological studies show that A. paniculata has a wide variety of pharmacological activities, including anti-inflammatory [5], antiviral [6], antibacterial [7], anticancer [8], hepatoprotective, hypertension [9,10] and platelet aggregation inhibition [11]. The pharmaceutical industry is now dealing with significant attrition rates of preclinical and clinical candidates due to toxicity or a lack of optimal pharmacokinetic properties, resulting in expensive and longer timelines for drug development [12]. ...
Andrographis paniculata, commonly known as the “King of Bitters” has traditionally been used as a medicinal herb. The metabolite composition of A. paniculata is generally determined by its properties, which may be influenced by a range of factors, one of which is the part of the plant extracted. The objective of this research is to identify and characterize the putative metabolite composition in n-hexane extract of stem and leaf using gas chromatography-mass spectrometry. A total of 22 different phytobioconstituents were identified, including flavonoids, terpenoids, fatty acids, phenolic acids, quinones, alkaloids and vitamin. The pharmacokinetic properties of the identified phytobioconstituents, like drug-likeness and toxicity, were also predicted by ADME/Tox analysis. Phytobioconstituents, predicted to be drug-like can be further investigated as ligands by using in silico docking approaches, for disease targets. The study provides empirical evidence for future study that might lead to their therapeutic applications and industrial product development.
... Andrographolide therapy reduced the levels of proinflammatory cytokines TNF, IL-1, and IL-6, as well as their related mRNA expression levels, in LPS-stimulated RAW264.7 cells. The andrographolides, which have shown antiinflammatory and immune-stimulatory properties, inhibit activation factors mediated by inflammatory response and also reduce expression of pro-inflammatory proteins [8]. In a previous study of in vivo anti-inflammatories, it was shown that TNF-α and GM-CSF release from mouse peritoneal macrophages were inhibited by andrographolide [9]. ...
Cytokine storm is a condition in which the immune system produces an excessive number of inflammatory signals, which can result in organ failure and death. It is also known as cytokine release syndrome, CRS, or simply cytokine storm, and it has received a lot of attention recently because of the COVID-19 pandemic. It appears to be one of the reasons why some people experience life-threatening symptoms from COVID-19, a medical condition induced by SARS-CoV-2 infection. In situations where natural substances can be exploited as therapeutics to reduce cytokine storm, the drug development process has come to the rescue. In the present study, we tested the potentiality of Andrographolide, labdane diterpenoid targeting several key cytokines that are secreted as a result of cytokine storm. We used molecular docking analyses, molecular dynamics simulations, and pharmacokinetic properties to test the stability of the complexes. The compound’s binding energy with some cytokines was over −6.5 Kcal/mol. Furthermore, a post-molecular dynamics (MD) study revealed that Andrographolide was extremely stable with these cytokines. The compound’s pharmacokinetic measurements demonstrated excellent properties in terms of adsorption, distribution, metabolism, and excretion. Our research revealed that this compound may be effective in lowering cytokine storm and treating severe symptoms.
... Given the growing evidence for the role of platelets in driving the progression of endometriosis [14,15,18,19,21] and for the hypercoagulant state in women with endometriosis [58][59][60], it is not surprising to see that platelet depletion and antiplatelet treatment effectively suppress lesion growth in mouse with induced endometriosis [14,20,49]. In addition, many compounds with therapeutic potentials in treating endometriosis [61], such as andrographolide [62,63], apigenin [64], scutellarin [50], tanshinone IIA [21,65], and wogonin [66], all have the commonality of being antiplatelet or anti-thrombotic [67][68][69][70][71]. Even some drugs that are known to be therapeutic for endometriosis or have therapeutic potentials, such as danazol [72] and valproic acid [73,74], are also antiplatelet/anti-thrombotic [75,76]. ...
The development of more efficacious, non-hormonal therapeutics for endometriosis is still an unmet medical need begging to be fulfilled. Growing evidence indicates that endometriotic lesions are wounds undergoing repeated tissue injury and repair, and, as such, platelets play an important role in lesional progression. Tetramethylpyrazine (TMP), a compound derived from a herb that has been used for thousands of years to combat “blood stasis” in traditional Chinese medicine, is a prescription drug in China for the treatment of cerebrovascular disorders. We tested the hypothesis that TMP can decelerate lesional progression through arresting epithelial-mesenchymal transition (EMT), fibroblast-to-myofibroblast transdifferentiation (FMT), and fibrogenesis. We found in our in vitro experiments that TMP treatment suppresses platelet-induced EMT, FMT, cellular contractility, and collagen production in a concentration-dependent manner. We also showed that in a mouse model of endometriosis, treatment with TMP significantly reduced lesion weight and the extent of lesional fibrosis and improved hyperalgesia, mostly likely through the reduction of lesional aggregation of platelets and the lesional expression of markers of EMT, FMT, and fibrogenesis. In light of our results and in view of its excellent safety profiles, TMP appears to be a promising drug candidate for treating endometriosis.
... In India, this plant is utilized in the form of decoction, juice, paste, powered of leaves, aerial parts, roots and whole plant for treatment of many types of fevers (chronic, malaria, typhoid and overheating) (Tiwari and Yadav, 2003;Sivasankari et al., 2014;Murtem and Chaudhry, 2016), upper respiratory infections (influenza, whooping cough, bronchitis and asthma) (Amroyan et al., 1999;Ayyanar and Ignacimuthu, 2005), snakebite/scorpion sting (Samy et al., 2008;Silambarasan and Ayyanar, 2015;Shivashankar et al., 2019), diabetes , dysentery/diarrhea (cholera) (Poonam and Singh, 2009), spleen enlargement, liver diseases (liver enlargement, jaundice) (Poonam and Singh, 2009;Zheng and Xing, 2009), skin diseases (skin infection, eczema, scabies, leprosy, skin allergies, itches and warts) (Suneetha et al., 2011), worm infections (ringworm, intestinal worms and ward off worms) (Ayyanar and Ignacimuthu, 2005), rheumatism (frozen joint and joint pain, gout and arthritis) (Vijayalakshme and Ranganathan, 2011), urinary disorder, piles, dripping of saliva, abdominal pain/body relaxing, body pain, kidney stones/calculi, tinea cruris, endogenous toxins, wounds, impotency, syphilis, HIV/AIDS, cancer and headache. It is also used as an antidote, blood purifier, febrifuge or anthelmintics, or debility/weakness tonic (Ayyanar and Ignacimuthu, 2005;Subramanian et al., 2012;Hu et al., 2017;Dai et al., 2019). ...
Ethnopharmacological relevance
Andrographis paniculata (Burm.f.) Nees is a medicinal herb of the Asian countries used in many traditional medicinal systems for the treatment of diarrhea, flu, leprosy, leptospirosis, malaria, rabies, upper respiratory infections, sinusitis, syphilis, tuberculosis and HIV/AIDS etc.
Aim of the study
This review aims to provide comprehensive, accurate and authentic information on traditional uses, photochemistry, and pharmacological properties of various extracts/fractions as well as phytocostituents of A. paniculata. In addition, this review also aims to provide advance and sensitive analytical methods along with chemical markers used in the standardization of herbal products for quality control (QC)/quality assurance (QA).
Materials and methods
All relevant publications were considered within the years 1983–2020. The publications were searched from Google Scholar, PubChem, Chemspider, PubMed, Elsevier, Wiley, Web of Science, China Knowledge Resource Integrated databases and ResearchGate using a combination of various relevant keywords. Besides, relevant published books and chapters were also considered those providing an overview of extant secondary literature related to traditional knowledge, phytochemistry, pharmacology and toxicity of the plant.
Results and Discussion
In this review, 344 compounds, including, terpenoid lactones, flavonoids, phenolic acids, triterpenes and volatile compounds were summarized out of which more than half of the compounds have no reported pharmacological activities yet. Terpenoid lactones and flavonoids are the major bioactive classes of compounds of A. paniculata which are responsible for pharmacological activities such as anticancer and antioxidant activities, respectively. Biosynthetic pathways and active sites for target proteins of both terpenoid lactones and flavonoids were considered. Analgesic, anticancer, antidiabetic, antifertility, antiinflammatory, antimalarial, antimicrobial, antioxidant, antipyretic, antiviral, antiretroviral, antivenom, cardioprotective, hepatoprotective, immunomodulatory and neuroprotective activities have been also reported. Andrographolide is a major characteristic active principle and responsible for most of the pharmacological activities. Therefore, andrographolide has been selected as a marker for the standardization of raw and marketed herbal products by TLC, HPTLC, HPLC, GC-MS, HPLC-MS and HPLC-MS/MS methods for QC/QA.
Conclusions
Conclusive evidence showed that the pharmacological activities reported in crude extracts and chemical markers are supporting and provides confidence in the traditional use of A. paniculata as a herbal medicine. The andrographolide could be used as a chemical marker for the QC/QA of raw and A. paniculata derived herbal products. Lactone ring in terpenoid lactone is an active site for targeted proteins. More efforts should be focused on the identification of the chemical markers from A. paniculata to provide a practical basis for QC/QA. Several aspects such as the mechanism of therapeutic potential, molecular docking technology and multi-target network pharmacology are very important for drug discovery and needed more investigation and should be considered. This compilation may be helpful in further study and QC/QA.
... The crude extract of A. paniculata was used for lowering the risk of damage to the heart muscle after myocardial infarction in rabbits in which the nitric oxide label is maintained by the plant and found effective in protecting endothelial functions [109] . Observation showed that in human the platelet activating factor (PAF) and eicosanoids are the main inflammatory mediators and the platelet activating factor is inhibited by andrographolide [110] . The clinical studies on rats showed anti-hyperglycemic effect of andrographolide in streptozotocin-induced diabetic rats [111] . ...
Abstract
Andrographis paniculata is an important medicinal plant of
Acanthaceae family and has widely known for its pharmacological
applications in Homeopathic, Ayurvedic, Chinese, Unani and traditional
systems of medicines. The plant is commercially grown throughout the
world such as India, Pakistan, Shri Lanka, China, South Asia and South
Africa due to its high demand in industries for medicinal purposes.
Terpenoids and flavonoids are the main phytoconstituents of the plant found
mainly in leaves and roots parts. Plant is well known for its vast
pharmacological properties such as anti-malarial, immune stimulatory, antidiarrheal, anti-thrombotic, anti-diabetic, anti-pyretic, anti-hyperlipidemic,
anti-venom, antiprotozoal, anti-viral, anti-oxidant, cardio-protective, gastroprotective, analgesic, anti-cancer, anti-fungal, anti-HIV, anti-diarrheal, and
anti-hypertensive activities. The main objective of present chapter is to sum
up its pharmacological potential, traditional knowledge and clinical studies
of plant.
Keywords: Andrographis paniculata, Acanthaceae, pharmacological
applications, terpenoids, flavonoids
... Andrographolide has a potent cardiovascular and antithrombotic activity (Amroyan et al. 1999). Crude water extract of Andrographis paniculata, its semi-purified butanol fraction and aqueous fraction possess cardiovascular activities contribute more to the hypotensive response than a direct action on the heart (Zhang and Tan 1997). ...
Andrographis paniculata (Burm.f) Nees (Family: Acanthaceae) is one of the most popular and valuable medicinal plants with high trade value. It is out mentioned in various systems of medicine since ancient times in Indian, Malay, Chinese and Thai. Andrographis paniculata is native to Southeast Asian countries i.e., India, China, Taiwan and Sri Lanka. In India it is distributed from Uttar Pradesh, West Bengal, Assam to Mizoram and also cultivated throughout the country. The plant being used as Ayurvedic medicine in various diseases.The principal chemical constituents are lactones, diterpenoid and flavonoids. Andrographolide, neoandrographolide are the principle secondary metabolites of Andrographis paniculata with more than 80 compounds reported till now. Modern studies revealed that Andrographis paniculata has an extensive range of pharmacological activities such as hepatoprotective, anti-inflammatory, antimalarial, antimicrobial, antidiarrhoeal, anti-human immunodeficiency virus (HIV), anti-oxidant and anti-pyretic. Therefore, such plants need value addition for product development.
... Andrographolide (Andro, Fig. 1a), a bicyclic diterpenoid lactone, has been reported to exhibit immunomodulatory, anti-inflammatory, cardioprotective, anti-tumour, anti-viral, antithrombotic, and hepatoprotective properties (Amroyan et al., 1999;Panraksa et al., 2017). In addition, microglial inhibitory activity through downregulation of NF-κB pathway in lipopolysaccharide (LPS)-stimulated macrophage and a rat model of stroke have been reported (Chan et al., 2010;Lee et al., 2011). ...
Cellular communication linking microglia activation and dopaminergic neuronal loss play an imperative role in the progression of Parkinson’s disease (PD); however, underlying molecular mechanisms are not precise and require further elucidation. NLR Family Pyrin Domain Containing 3 (NLRP3) inflammasome activation is extensively studied in context to microglial activation and progressive dopaminergic neuronal loss in PD. Several pathophysiological factors such as oxidative stress, mitochondrial dysfunction impaired mitophagy plays a crucial role in activating NLRP3 inflammasome complex. Hence, regulation of microglial activation through mitophagy could be a valuable strategy in controlling microglia mediated neurodegeneration. In this study we have developed a model of inflammasome activation by combining LPS with a mitochondrial complex-I inhibitor MPP+. The idea of using MPP+ after priming mouse microglia with LPS was to disrupt mitochondria and release reactive oxygen species, which act as Signal 2 in augmenting NLRP3 assembly, thereby releasing potent inflammatory mediators such as active interleukin-1 beta (IL-1β) and IL-18. LPS-MPP+ combination was seen to impaired the mitophagy by inhibiting the initial step of autophagosome formation as evidenced by protein expression and confocal imaging data. Treatment with Andrographolide promoted the parkin-dependent autophagic flux formation in microglia; resulting in the removal of defective mitochondria which in turn inhibit NLRP3 inflammasome activation. Additionally, the neuroprotective role of Andrographolide in inhibiting NLRP3 activation together with salvage ATP level via promoting parkin-dependent mitophagy was seen in the substantial nigra par compacta (SNpc) region of mice brain. Furthermore, Andrographolide rescued the dopaminergic neuron loss and improved the behavioural parameters in animal model. Collectively, our results reveal the role of mitophagy in the regulation of NLRP3 inflammasome by removing defective mitochondria. In addition, andrographolide was seen to abate NLRP3 inflammasome activation in microglia and rescue dopaminergic neuron loss.
... A. paniculata has been reported to possess antibacterial, antifungal, antiviral, hypoglycemic, anti-cancer, anti-inflammatory and antipyretic properties [12]. The major modern use of A. paniculata is for the prevention and treatment of cold as it possesses antithrombotic actions, suggesting a likely advantage in cardiovascular disease [13]. ...
... The leaves of Andrographis paniculata, popular in Scandinavia as a cold and influenza remedy, are used traditionally in Ayurvedic, Thai and Chinese medicine to treat fever associated with infectious diseases. Pharmacological studies suggest anti-inflammatory [33] [34], antipyretic [35] [36], antiviral [37] and immunostimulatory [38] properties. The aim of this review was to systematically assess Andrographis paniculata has the most antiviral inhibitory effects. ...
This research of study continues personal research and professional practice in the Alternative Medicine (AM) has become an attractive and a popular issue between academicians and researchers in the last decades. AM is mostly used by individuals to support or to substitute the medical treatment. The
studies from different disciplines have shown that the AM use is expanding all over the world but the popularity and the types of its use remain unclear. A qualitative study was conducted by treating a patient through several kinds of AM, receiving positive feedback from the patient. The overall data shows very good improvement since the AM becomes one of their parts of life to
continue surviving on this earth with lots of challenges. Herbalist and vitamin supplements are the most popular and commonly used alternative medicine methods. Most people had used alternative medicine to improve their health conditions, thus eliminating the side effects of modern treatments. To supersede
and recover or heal this chronic symptom, a combination of AM will be great to encounter it such as cancer, psoriasis, epilepsy, viral fever, etc. A combination of Ganotherapy and Knowledge of Holistic Human System enhances the AM era into battling these chronic cases and creates a powerful immune system to protect against it.
... The observed results suggest that the other new compounds like two flavanoids such as andropaniculosin A and ropaniculoside A present in the extracts may be responsible and attributed for high anti-platelet activity [71]. To support further, a study by Amroyan et al. [72] has shown that andrographolide inhibits PAF-induced human blood platelet aggregation in a dose-dependent manner. However, study results suggest that the mechanism of action of andrographolide is entirely different from a known NSAIDs action. ...
Dengue is a debilitating disease that poses a perpetual threat to human health and increases the global economic burden every year. Despite advances in medical sciences, dengue virus (DENV) infects approximately 200 million people every year. To date, no effective antiviral is valiable to treat DENV in individuals despite great efforts in accomplishing these goals. Numerous approaches have been used in the search for dengue antiviral like screening of combinatorial compounds against DENV enzymes and structure-based computational discovery. In recent years, investigators have turned their focus into medicinal plants, trying to identify compounds that can be used as dengue antiviral. Nature represents a great reservoir of potential substances that can be explored with the aim of discovering new drugs that can be either used directly as pharmaceuticals or can provide drug leads, which can be scrutinized further for the development of new anti-dengue natural product. Many previous investigations have dealt with numerous plant extracts or bioactive principles for their antiviral property as they normally considered being safer when compared to synthetic drugs. Andrographis paniculata belongs to family Acanthaceae and is generally known as 'king of bitters'. Diverse bioactive compounds from this plant such as diterpenes, flavonoids, xanthones, noriridoides and other miscellaneous compounds have exhibited their potential as therapeutics for various chronic as well as infectious diseases. This review is based on literature review on scientific journals, books and electronic sources, which highlights the pathogenesis of DENV and describe an assortment of bioactive principles that have been possessing antiviral potential, which include dengue and discuss the therapeutic efficacy and mechanism of action of Andrographis paniculata. However, a detailed and more comprehensive clinical trial on mammalian tissues and organs is needed in future studies. © 2020 Asian Pacific Journal of Tropical Medicine Produced by Wolters Kluwer-Medknow. All rights reserved.
... The results indicated that the standardized Andrographis paniculata extract may contain other anti-platelet compounds, which contribute to high anti-platelet activity. Amroyan, et al [80] tested andrographolide for PAF-induced platelet aggregation, where, andrographolide inhibited PAF-induced human blood platelet aggregation in a dose dependent manner (IC50 ~5 μM). These results indicated that andrographolide has a mechanism of action different from that of non-steroidal anti-inflammatory drugs (NSAID) and most likely associated with the cardiovascular and antithrombotic activity described of Andrographis paniculata. ...
Andrographis paniculata is widely cultivated and its importance as a medicinal plant is growing up with stronger reports in support of its multifarious therapeutic uses. Taking great concern of the useful benefits of the plant, it can be advocated as a safe, highly important medicinal plant for mankind. This herb contains a large number of chemical constituents, mainly lactones, diterpenoids, diterpene glycosides, flavonoids and flavonoid glycosides. It has multiple pharmacological properties such as antibacterial, hepatoprotective activity, anti-cancer, antitumor, hypoglycemic, immunomodulatory and hypotensive activities. The earlier and current status of therapeutic usage, phytochemistry, pharmacological activity and toxicity profile research on Andrographis paniculata has been described in this review as to bridge the gap required for the coming research opportunities in future. It also emphasizes at compiling vast pharmacological applications to make the potential image of Andrographis paniculata as a multipurpose medicinal agent. The extracts and metabolites of this plant did not show any kind of significant acute toxicity in experimental animals.
... Basically phytochemicals are divided into two groups that are primary and secondary metabolites based on the function in plant metabolism. Primary metabolites are comprise common carbohydrates, amino acids, proteins and chlorophylls while secondary metabolites consist of alkaloids, saponins, steroids, flavonoids and tannins in Andrographis spp., all of which are responsible for various biological activities (Chakravarti and Chakravarti 1951;Kirtikar and Basu, 1975;Amroyan et al., 1999;Niranjan et al., 2010;Rajalakshmi et al., 2012;Savithramma et al., 2012;Neeraja et al., 2014). ...
Andrographis is an important genus of the family Acanthaceae known for its ethnomedicinal claims and for a variety of medicinal properties. The current review briefly summarizes the distribution, phytochemical components, biological and pharmacological activities of Andrographis spp. distributed in Southern Eastern Ghats, South India along with colour photographs of important species. More than 10 species of Andrographis are distributed in Southern Eastern Ghats, South India which includes A. affinis, A. alata, A. beddomei, A. elongata, A. echioides, A. glandulosa, A. lineata, A. ovata, A. paniculata and A. serpyllifolia. Among the different species of Andrographis, only some are studied for their biological and pharmacological activities. The phytochemical components in Andrographis spp. responsible for the biological and pharmacological activities reported in various studies are andrographolide, neoandrographolide, 14-deoxy- 11,12-didehydroandrographolide, 14-deoxy-andrographolide, andrographiside and serpyllin. The important pharmacological effects of Andrographis spp. and their derivatives include the activities like antidiabetic, anticancer, antifertility, anti-inflammatory, antioxidant, antivenom, hepatoprotective, immunomodulatory, antimicrobial, antipyretic, anthelmintic and antiviral (against chikungunya) activity.
... It also affects important inflammatory mediators, such as eicosanoids and plateletactivating factor (PAF) in a dose-dependent manner (IC50~5µM). 27 Another major phytoconstituent of AP, 14-Deoxy-11,12didehydroandrographolide, significantly inhibited the expression of proinflammatory cytokines/chemokines ( TNF-α, IL-1β, IL-6, CCL-2/MCP-1, IFN-α, IFN-β, IFN-γ, MIP-1α, MIP-1β in lungs of mice infected with pathogenic influenza viruses, H5N1. 28 ...
... Its medicinal uses have included the treatment of a variety of inflammation diseases such as diarrhea, fevers, laryngitis, gastric infections and upper respiratory tract infections, as well as other chronic and infectious disorders (Lim et al., 2012). A. paniculata has been included in the WHO monographs on selected medicinal plants (World Health Organization, 2002), where it was reported that the plant was considered highly efficacious in inhibiting the spread of the influenza epidemic of 1919 in India (Amroyan et al., 1999;Avani and Rao, 2008;Lim et al., 2012;Sudhakaran, 2012;Sc, 2014). Phytochemical data show that A. paniculata can produce high quantities of biologically active ent-labdane-type diterpenoids and flavones, such as andrographolide, neoandrographolide, and andrographidine A, B and C (Koteswara Rao et al., 2004;Wang et al., 2009;Chao and Lin, 2010;Ma et al., 2010;Subramanian et al., 2012). ...
Andrographis paniculata is a herbaceous dicot plant widely used for its anti‐inflammatory and anti‐viral properties across its distribution in China, India and other Southeast Asia countries. A. paniculata was used as a crucial therapeutic treatment during the influenza epidemic of 1919 in India and is still used for the treatment of infectious disease in China. A. paniculata produces large quantities of the anti‐inflammatory diterpenoid lactones andrographolide, neoandrographolide and their analogs; touted to be the next generation of natural anti‐inflammatory medicines for lung diseases, hepatitis, neurodegenerative disorders, autoimmune disorders and inflammatory skin diseases. Here, we report a chromosome‐scale A. paniculata genome sequence of 269 Mb that was assembled by Illumina short reads, PacBio long reads and Hi‐C data. Gene annotation predicted 25,428 protein‐coding genes. To decipher the genetic underpinning of diterpenoid biosynthesis, transcriptome data from seedlings elicited with methyl jasmonate also was obtained, which enabled identification of genes encoding diterpenoid synthases, cytochrome P450 monooxygenases, 2‐oxoglutarate‐dependent dioxygenases and UDP‐dependent glycosyltransferases potentially involved in diterpenoid lactone biosynthesis. We further carried out functional characterization of pairs of classes I and II diterpene synthases, revealing the ability to produce diversified labdane‐related diterpene scaffolds. In addition, a glycosyltransferase able to catalyze O‐linked glucosylation of andrograpanin, yielding the major active product neoandrographolide, was identified as well. Thus, our results demonstrate the utility of the combined genomic and transcriptomic dataset generated here for investigation of the production of the bioactive diterpenoid lactone constituents of the important medicinal herb A. paniculata.
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... Th e theurapeutic benefi t of this herb has been attributed to adographolide (alkaloid) and its related diterpenoid compound, i.e. deoxandographolide and neonandrographolide (ICH Committee 1996;Bunyaprapatrasara & Chokecharocopons 1997). Pharmaceutical studies suggest anti-infl ammatory (Shen et al. 2002;Amroyan et al. 1999), antipyretic (Madav et al. 1995, antiviral (Chang et al. 1991), immunostimulaory (Puri et al. 1993), potential cancer therapeutic agent (Rajgopal et al. 2003), antihyperglycemic (Bu-Chin et al. 2003) and antioxidant (Zhang & Tan 2000) properties. ...
Kalmegh (Andrographis paniculata Nees.) is an important medicinal plant which is employed in the Indian traditional system of medicine (Folk medicine), Homeopathy, Ayurveda and Unani system of medicine. Its leaves, stem and infl orescence are used as medicine. Its major bitter principles are diterpenoids -andrographolide and neo-andrographolide. It is useful in the treatment of liver disorders, hepatitis, dysentery, febrifuge etc. Th e herb kalmegh is also used as a liver tonic, in hyperdispsia, wounds, ulcers, chronic fever, malarial and intermittent fevers, infl ammations, coughs, bronchitis, skin diseases, leprosy, colic, fl atulence, diarrhoea, dysentery, haemorrhoids. Th is study of germination revealed that germination was essentially complete aft er 16 d. KNO 3 and GA 3 improved the seed germination percentage. Germination in the presence of NaHClO 3 was rapid, taking only 8 d. Being a medicinal plant, KNO 3 and NaHClO 3 treatments are economic and easily applied by nursery workers and poor farmers in developing mass planting stocks.
... Various preparations and compound formulas of the herb have been used to treat infectious and non-infectious diseases, with significant effective rates reported for conditions such as epidemic encephalitis B, suppurative otitis media, neonatal subcutaneous annular ulcer, vaginitis, cervical erosion, pelvic inflammation, herpes Modern application-Modern application of A. paniculata is for the prevention as well as for the treatment of the common cold. It also has antithrombotic properties and recommending in cardiovascular disease [22] . Several Pharmacological and clinical studies indicating the potential for beneficial effects in diseases like cancer and HIV infections [23,24] . ...
... A. paniculata is one of the most commonly used medicinal plants in the traditional systems of Unani and Ayurvedic medicines. 1 A. paniculata is reported to exhibit a broad range of pharmacological effects such as immunostimulant, 2 antimicrobial, 3 anti-inflammatory, 4 hypotensive, 5 antihyperglycemic, 6,7 atherosclerotic, 8 antimalarial, 9 anti-HIV, 10 antiplatelet aggregation, 11 hepatic lipid peroxidation protective, 12 hepatoprotective, 13 choleretic, 14 and anticancer effects. [15][16][17] Andrographolide is the major labdane diterpenoid isolated from A. paniculata and exhibits both in vitro as well in vivo anti-inflammatory and anticancer activities. ...
Andrographolide, a bioactive compound isolated from Andrographis paniculata exhibits multiple pharmacological activities, including anti-HIV, antiplatelet aggregation, hepatic lipid peroxidation protective, hepatoprotective, choleretic, and anticancer effects. Herein, we report the synthesis of diverse analogues of andrographolide along with their β-glucosidase inhibitory activity against sweet almond β-glucosidase. The parent compound, And-1, displayed moderate inhibitory activity against the sweet almond β-glucosidase with IC50 of 142.5 μM. Among the synthesised analogues And-10 showed the best activity, with IC50 of 92.4 μM, whereas the oxidised products (And-4 and And-5) were moderately active against the tested enzyme. Additionally, compounds And-6, And-7, And-8, and And-10 exhibited better β-glucosidase inhibitory activity than the positive control Castanospermine, with IC50 of 100.2, 102.4, 106.5, and 92.4 μM, respectively. These results highlight the importance of an electron-withdrawing NO2 group on the phenyl moiety in attaining the better β-glucosidase inhibition. It is noteworthy that the effect of a particular group plays a significant role in bioactivity. This study thus highlights an important aspect with regard to the most active compounds, which could extend the arsenal of compounds affecting the corresponding enzymes after further polishing and fine tuning.
... While methanol extract showed moderate (68% inhibition at 1.25 mg/ ml) and dose-dependent inhibition, aqueous extract did not impair swarming motility. At all measured time points (16,24 and 48 h), the mean swarming diameters in presence of sub-MIC (1.25 mg/ml) levels of both chloroform and methanol extracts were significantly less compared to those of drug-free vehicle controls. Moreover, chloroform extract completely blocked swarming motility, even when plates were incubated up to 48 h (Fig. 4b). ...
Quorum-sensing (QS) is known to play an essential role in regulation of virulence factors and toxins during Pseudomonas aeruginosa infection which may frequently cause antibiotic resistance and hostile outcomes of inflammatory injury. Therefore, it is an urgent need to search for a novel agent with low risk of resistance development that can target QS and inflammatory damage prevention as well. Andrographis paniculata, a herbaceous plant under the family Acanthaceae, native to Asian countries and also cultivated in Scandinavia and some parts of Europe, has a strong traditional usage with its known antibacterial, anti-inflammatory, antipyretic, antiviral and antioxidant properties. In this study, three different solvent extracts (viz., chloroform, methanol and aqueous) of A. paniculata were examined for their anti-QS and anti-inflammatory activities. Study was carried out to assess the effect on some selected QS-regulatory genes at transcriptional level using Real Time-PCR. In addition, ability to attenuate MAPK pathways upon P. aeruginosa infection was performed to check its potential anti-inflammatory activity. Chloroform and methanol extracts showed significant reduction (p < 0.05) of the QS-controlled extracellular virulence factors in P. aeruginosa including the expression of pyocyanin, elastase, total protease, rhamnolipid and hemolysin without affecting bacterial viability. They also significantly (p < 0.05) reduced swarming motility and biofilm formation of P. aeruginosa. The chloroform extract, which was found to be more effective, decreased expression of lasI, lasR, rhlI and rhlR by 61%, 75%, 41%, and 44%, respectively. Moreover, chloroform extract decreased activation of p-p38 and p-ERK1/2 expression levels in MAPK signal pathways in P. aeruginosa infected macrophage cells. As the present study demonstrates that A. paniculata extracts inhibit QS in P. aeruginosa and exhibit anti-inflammatory activities, therefore it represents itself as a prospective therapeutic agent against P. aeruginosa infection.
... So scientist interest is renewed in traditional systems of medicine to find out effective, safer and cheaper remedy for animals and humans. In this context it had been shown in several animal studies that extracts of Andrographis paniculata and its constituents, namely the diterpene lactone andrographolide, have anti-inflammatory properties and possibly associated with the inhibition of the PAF-mediated inflammatory response (Amroyan et al., 1999) and the inhibition of nitric oxide synthesis in macrophages (Chiou et al., 1998). Most of pharmacokinetic and anti-inflammatory studies of andrographolide were conducted following oral and intravenous route. ...
... No clinical cases reported (Williamson et al. 2013). Based on animal models, possible interaction with antiplatelet (inhibit platelet aggregation) (Amroyan et al. 1999) and antidiabetic drugs (possible hypoglycemic effect) (Husen et al. 2004). It might cause decrease of fertility at high doses; thus, patients undergoing infertility treatment should avoid this herb (Kligler et al. 2006). ...
This chapter presents indications, clinical evidence, pre-clinical evidence, mechanisms of action, interactions, and contraindications of Kalmegh (Andrographis paniculata). Kalmegh is mainly used to treat infection, inflammation and fever, and specifically the common cold, influenza type and other upper respiratory tract infections (URTIs). In both Chinese medicine and Ayurveda, it is used for a wide range of complaints including cardiovascular disorders, and as a general tonic. Adverse effects, dosage, and general plant information are included in the chapter. The plant is native to India, China, and Southeast Asia. It is a commonly used plant in Chinese traditional medicine as well as the Unani and Ayurvedic systems.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), also known as COVID-19, is currently developing into a rapidly disseminating and an overwhelming worldwide pandemic. In severe COVID-19 cases, hypercoagulability and inflammation are two crucial complications responsible for poor prognosis and mortality. In addition, coagulation system activation and inflammation overlap and produce life-threatening complications, including coagulopathy and cytokine storm, which are associated with overproduction of cytokines and activation of the immune system; they might be a lead cause of organ damage. However, patients with severe COVID-19 who received anticoagulant therapy had lower mortality, especially with elevated D-dimer or fibrin degradation products (FDP). In this regard, the discovery of natural products with anticoagulant potential may help mitigate the numerous side effects of the available synthetic drugs. This review sheds light on blood coagulation and its impact on the complication associated with COVID-19. Furthermore, the sources of natural anticoagulants, the role of nanoparticle formulation in this outbreak, and the prevalence of thrombosis with thrombocytopenia syndrome (TTS) after COVID-19 vaccines are also reviewed. These combined data provide many research ideas related to the possibility of using these anticoagulant agents as a treatment to relieve acute symptoms of COVID-19 infection.
Andrographis paniculata is an annual medicinal herb from the family Acanthaceae. Andrographolide is generally considered an essential bioactive component of plant Andrographis paniculata. Since ancient times, it has been widely recognized for its therapeutic qualities and has attracted the scientific and medical communities' attention. This review summarizes the molecular, clinical, and in vitro research of compound andrographolide and its mechanism of action. Andrographolide, when combined with other enhancing agents, offers a wide variety of health benefits. The therapeutic potential of andrographolide has been exemplified and exhibited by directly regulating genes and indirectly interacting with small molecules and different enzymes. This review compiles and consolidates the pharmacological action of andrographolide and its analogs and decipher the gaps that have hindered its use in medicinal research.
Andrographis paniculata (Burm.f.) Nees is an essential traditional herbal medicine with various bioactivities in Asian countries. The quality of herbal medicines directly affects its clinical efficacy, so a comprehensive strategy, including color assay, chemical profiles, quantitative analysis, and anti-inflammatory activity assay, is constructed to evaluate the quality of A. paniculata in this paper. Here, 16 batches of commercial A. paniculata were collected, and there were noticeable differences in appearance, chemical compounds, and bioactivity among batches. Principal component analysis (PCA) both indicated the color and diterpenoid lactones could be used to classify A. paniculat. And then, correlation analysis found the batches with greener color have higher contents of diterpenoid lactones and more efficient anti-inflammatory activity. Based on the results above, the partial least squares (PLS) regression models were finally established to predict the contents of diterpenoid lactones using the color assay data. All diterpenoid lactones models showed good performance, especially neoandrographolide. Notably, PLS regression models were first used for the nondestructive quality evaluation of A. paniculata. This comprehensive quality evaluation strategy can theoretically elucidate the relationship between good appearance, high contents of diterpenoid lactones, and superior bioactivity of A. paniculata, which is meaningful for its quality control and evaluation. It also laid a theoretical basis for appearance and bioactivity evaluations of high-quality traditional herbal medicine.
COVID-19, the disease caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in 2019 and has infected over 230 million people worldwide as of October 1, 2021. Common initial signs and symptoms include cough, fever, fatigue, headache, muscle aches and pain, and diarrhea [2]. Some individuals with COVID-19 become severely ill, usually starting about 1 week after symptom onset; severe COVID-19 often involves progressive respiratory failure and may also result in life-threatening pneumonia, multiorgan failure, and death. In addition, thousands of individuals-possibly 10% to 75%-who have had COVID-19 report symptoms of “long COVID” (including fatigue, muscle weakness, sleep difficulties, and cognitive dysfunction) for several months after the acute stage of illness has passed.
Currently, data are insufficient to support recommendations for or against the use of any vitamin, mineral, herb or other botanical, fatty acid, or other dietary supplement ingredient to prevent or treat COVID-19. And by law, dietary supplements are not allowed to be marketed as a treatment, prevention, or cure for any disease; only drugs can legally make such claims. Nevertheless, sales of dietary supplements marketed for immune health increased after the emergence of COVID-19 because many people hoped that these products might provide some protection from SARS-CoV-2 infection and, for those who develop COVID-19, help reduce disease severity.
The immune system defends the body against pathogens that cause disease and is comprised of innate responses, which are the first line of defense, and adaptive responses, which become engaged later.
Andrographis paniculata Nees is a plant that has been effectively used in traditional Asian medicines for centuries. It's perceived "blood purifying" property and also for medicinal properties. The present paper deals to study the phytochemical screening of Andrographis paniculata for various medicinally important compounds. In the present investigation, it was found that phenols, alkaloids, tannins, flavonoids are present in leaves, stem, and root of the plant. Saponin is absent.
Aim
Andrographolide, the major bioactive compound of the plant Andrographis paniculata, exerts anti-inflammatory, cyto-, neuro- and hepato-protective effects. Traditional remedies for infectious diseases include A. paniculata for maladies like fever, pain, rashes which are associated with chikungunya and other arboviral diseases. Since andrographolide and A. paniculata have potent antiviral properties, the present review aims to provide a comprehensive report of symptoms and immunological molecules involved in chikungunya virus (CHIKV) infection and the therapeutic role of andrographolide in the mitigation of chikungunya and associated symptoms.
Materials and methods
Studies on the therapeutic role of A. paniculata and andrographolide in chikungunya and other viral infections published between 1991 and 2021 were searched on various databases.
Results and discussion
The havoc created by chikungunya is due to the associated debilitating symptoms including arthralgia and myalgia which sometimes remains for years. The authors reviewed and summarized the various symptoms and immunological molecules related to CHIKV replication and associated inflammation, oxidative and unfolded protein stress, apoptosis and arthritis. Additionally, the authors suggested andrographolide as a remedy for chikungunya and other arboviral infections by highlighting its role in the regulation of molecules involved in unfolded protein response pathway, immunomodulation, inflammation, virus multiplication, oxidative stress, apoptosis and arthritis.
Conclusion
The present review demonstrated the major complications associated with chikungunya and the role of andrographolide in alleviating the chikungunya associated symptoms to encourage further investigations using this promising compound towards early development of an anti-CHIKV drug.
Chemical Compound studied: andrographolide (PubChem CID: 5318517)
Myocardial infarction (MI) is the irreversible injury of the myocardium caused by prolonged myocardial ischemia and is a major cause of heart failure and eventual death among ischemic patients. The present study assessed the protective potentials of andrographolide against isoproterenol-induced myocardial infarction in rats. Animals were randomly divided into four groups: Control (Ctr) group received 0.9 % saline solution once daily for 21 days, Isoproterenol (Iso) group received 0.9 % saline solution once daily for 19 days followed by 80 mg/kg/day of isoproterenol hydrochloride solution on day 20 and 21, Andrographolide (Andro) group received 20 mg/kg/day of andrographolide for 21 days, and Andrographolide plus Isoproterenol (Andro + Iso) group received 20 mg/kg/day of andrographolide for 21 days with co-administration of 80 mg/kg/day of isoproterenol hydrochloride solution on day 20 and 21. After all treatments, cardiac-specific parameters that define cardiac health and early subacute MI were measured in all groups using both biophysical and pharmacological assay methods. Isoproterenol administration significantly (p<0.05) increased cardiac mass indexes, systemic cardiac biomarkers, infarct size and caused cardiac histological alterations; significantly (p<0.05) increased heart rate, QRS & QTc intervals and caused ST-segment elevation; significantly (p<0.05) increased myocytes shortening, action potential duration (APD), L-type Ca²⁺ current (ICa,L) density and significantly (p<0.05) decreased transient outward K⁺ current (Ito) density typical of the early subacute MI. Interestingly, pretreatment with andrographolide prevented and or minimized these anomalies, notably, by reducing ICa,L density and increasing Ito density significantly. Therefore, andrographolide could be seen as a promising therapeutic agent capable of making the heart resistant to early subacute infarction and it could be used as template for the development of semisynthetic drug(s) for cardiac protection against MI.
This study aimed at carrying out a preformulation investigation of nanocochleates (NCs) and develop andrographolide-loaded nanocochleates. Preformulation study comprised of exploring the effect of trivalent and divalent ions on transition temperature (TT) of lipid (DMPG-Na), on particle size (PS), entrapment efficacy (EE), zeta potential (ZP) of NCs, and effect of NCs on change in lipid solubility post-NC formation. Further, the andrographolide-loaded nanocochleates made with CaCl2 (ANDNCs) were characterized for ZP, PS, EE, X-ray powder diffraction (PXRD), differential scanning calorimetry (DSC), transition electron microscopy (TEM), in vitro release studies, in vitro anticancer potential on the cell line of human breast cancer (MCF-7), in vivo oral pharmacokinetic studies, and tissue distribution in female Wistar rats. Nanocochleates developed with CaCl2 had a significant reduction in PS (1.78-fold) and ZP (1.38-fold), and elevation of EE (1.17-fold) as compared to AlCl3 developed NCs. Trivalent ions demonstrated elevation of TT as compared to divalent ions. Spiral-shaped ANDNCs demonstrated ZP, PS, and EE of - 121.46 ± 15.12 mV, 360 ± 47 nm, and 68.12 ± 3.81% respectively. In vitro release study of ANDNCs showed a strong pH-dependent release profile due to hydrogen bonding between NCs and andrographolide (AND). Formulated ANDNCs demonstrated 26.99-fold decrease in IC50 value as compared to free AND. Additionally, the oral bioavailability of AND from ANDNCs improved by 1.81-fold as compared to free AND. Furthermore, ANDNCs showed minimum accumulation within the vital organs such as liver, kidney, and spleen. Briefly, the preformulation study laid a platform for better understanding the NCs and its components. Further, developed ANDNCs revealed superior physiochemical properties to be used as an alternative for a clinical setting.
Cellular communication linking microglia activation and dopaminergic neuronal loss play an imperative role in the progression of Parkinson's disease (PD); however, underlying molecular mechanisms are not precise and require further elucidation. NLR Family Pyrin Domain Containing 3 (NLRP3) inflammasome activation is extensively studied in context to microglial activation and progressive dopaminergic neuronal loss in PD. Several pathophysiological factors such as oxidative stress, mitochondrial dysfunction impaired mitophagy plays a crucial role in activating NLRP3 inflammasome complex. Hence, regulation of microglial activation through mitophagy could be a valuable strategy in controlling microglia mediated neurodegeneration. In this study we have developed a model of inflammasome activation by combining LPS with a mitochondrial complex-I inhibitor MPP+. The idea of using MPP+ after priming mouse microglia with LPS was to disrupt mitochondria and release reactive oxygen species, which act as Signal 2 in augmenting NLRP3 assembly, thereby releasing potent inflammatory mediators such as active interleukin-1 beta (IL-1β) and IL-18. LPS-MPP+ combination was seen to impaired the mitophagy by inhibiting the initial step of autophagosome formation as evidenced by protein expression and confocal imaging data. Treatment with Andrographolide promoted the parkin-dependent autophagic flux formation in microglia; resulting in the removal of defective mitochondria which in turn inhibit NLRP3 inflammasome activation. Additionally, the neuroprotective role of Andrographolide in inhibiting NLRP3 activation together with salvage ATP level via promoting parkin-dependent mitophagy was seen in the substantial nigra par compacta (SNpc) region of mice brain. Furthermore, Andrographolide rescued the dopaminergic neuron loss and improved the behavioural parameters in animal model. Collectively, our results reveal the role of mitophagy in the regulation of NLRP3 inflammasome by removing defective mitochondria. In addition, andrographolide was seen to abate NLRP3 inflammasome activation in microglia and rescue dopaminergic neuron loss.
The aim of our review is to demonstrate the potential of herbal preparations, specifically adaptogens for prevention and treatment of respiratory infections, as well as convalescence, specifically through supporting a challenged immune system, increasing resistance to viral infection, inhibiting severe inflammatory progression, and driving effective recovery. The evidence from pre-clinical and clinical studies with Andrographis paniculata, Eleutherococcus senticosus, Glycyrrhiza spp., Panax spp., Rhodiola rosea, Schisandra chinensis, Withania somnifera, their combination products and melatonin suggests that adaptogens can be useful in prophylaxis and treatment of viral infections at all stages of progression of inflammation as well as in aiding recovery of the organism by (i) modulating innate and adaptive immunity, (ii) anti-inflammatory activity, (iii) detoxification and repair of oxidative stress-induced damage in compromised cells, (iv) direct antiviral effects of inhibiting viral docking or replication, and (v) improving quality of life during convalescence.
For thousands of years, medicinal plants have been used by mankind to treat numerous disease conditions including metabolic syndrome. In addition to common usage as herbs, spices, fruits, and beverages, there is now also a growing trend to employ many medicinal plants as dietary supplements. This chapter outlines the chemical and pharmacological basis of antidiabetic medicinal plants now rebranded as dietary supplements. It critically assesses the scientific evidences for the therapeutic potentials of Aloe vera (L.) Burm. f., Andrographis paniculata (Burm. F.), Wall. Ex Nees, banaba (Lagerstroemia speciose (L) Pers), Cassia and Senna species including Senna auriculata (L) Roxb, S. alata (L.) Roxb., Ginkgo biloba L., ginseng (Panax. ginseng C.A. Mey, P. quinquefolius L., and P. notoginseng), aymnema (Gymnema sylvestre (Retz.) R.Br. ex Sm.), Jamun (Syzygium cumini (L.) Skeels), olive leaf extract (Olea europaea (L.)), Scutellaria (Scutellaria baicalesis Georgi), and St John's wort (Hypericum perforatum L.).
Despite the demonstrated efficacy of surgical treatment of endometriosis, recurrence after surgery still remains a formidable challenge. Surgery, especially when performed repeatedly, decreases ovarian reserve. Clearly, control of recurrence is an unmet medical need. So far nearly all efforts to control recurrence have been devoted to the identification of risk factors, biomarkers, and postoperative medication. One area that has been completely overlooked is the possibility of perioperative intervention. In this study, we tested the hypothesis that perioperative use of a nonspecific β-blocker and/or a nuclear factor-κB (NF-κB) inhibitor can retard the growth of residual endometriotic lesions that are left intact in the primary surgery. We established a mouse model of recurrence due to incomplete lesion removal by deliberately leaving residual lesions intact in the primary excision surgery. One hour before and 24 hours after the surgery, mice were either untreated or treated with andrographolide, propranolol, or both. Two weeks after the primary surgery, all mice were sacrificed and all lesions were excised and evaluated for immunohistochemistry analysis. We found that perioperative use of andrographolide and/or propranolol significantly decelerated the growth of residual lesions that were intentionally left out during the primary surgery. The perioperative intervention also significantly attenuated the generalized hyperalgesia resulting from the presence of residual lesions. It also inhibited the activation of the adrenergic receptor β2 signaling, resulting in reduced angiogenesis, epithelial–mesenchymal transition, fibroblast-to-myofibroblast transdifferentiation as well as NF-κB suppression and progesterone receptor isoform B induction. These data strongly suggest that perioperative use of β-blockers and/or NF-κB inhibitors may reduce the risk of recurrence in endometriosis.
Selenohalides of Rhodium and their thermal decomposition products, synthesized in non-aqueous inorganic selenochloride media, without using expensive templates may be promising active components of electrocatalysts and heterogeneous catalysts. In these systems, the activation and the transformation of reactants take place not only on the central rhodium atoms, but also on chalcogenide units. In contrast to thermally unstable organic complexes, rhodium selenohalides are thermally stable up to 300-350°C, and products of their thermal decomposition, up to 900°C, which makes substantially wider the range of their practical application in catalysis. The specific structure features of these compounds and their thermodestruction products suggest that these systems may possess not only the redox, but also the acid properties, exhibiting bifunctionality. Solids based on rhodium selenochlorides show catalytic activity in the methane oxidative carbonylation and are no carbonized during the reaction. Methanol, methyl acetate and acetic acid are the main products of the process. The process selectivity depends mainly on the rhodium selenochloride composition and the type of silica used for catalyst preparation. Catalytic properties of gallium-modified zeolite Ga/H-ZSM-5 promoted by rhodium selenochlorides studied in the glycerol conversion to oxygen-containing chemicals: acrolein, allyl alcohol and acetaldehyde. It was shown that the promotion of Ga/H-ZSM-5 by the product of the thermal decomposition of Rh2Se9Cl6 results in the higher yield of the acrolein.
SEA, a mixture of succinoyl ester derivatives of andrographolid, previously shown to be the first in vitro nonpeptide inhibitor of Proprotein Convertases (PC) PC1, furin, and PC7 [Basak, et al., Biochem. J. 1999; 338: 107–113] has been tested ex vivo for its anti-Proprotein Convertase (PC) activity. SEA blocks PC-mediated cleavages of proBDNF (Brain Derived Neurotrophic Factor) (RVRR¹²⁸↓HS) and surface envelope glycoprotein gp160 of HIV (RERR⁵¹¹↓AV) in a dose dependent manner. 25 μM of SEA completely blocks the cleavage of 32 kDa proBDNF into its 14 kDa mature form while 75 μM prevents significantly HIV gp160 processing into gp41. The estimated IC50 value for the latter is ∼ 40 μM. At higher concentration, SEA is partly cytotoxic to the cells, with less protein secretion in culture medium. In an effort to examine further, the anti-PC activity of SEA and other andrographolid products, we examined their effects on human leukemic cell growth. Data showed a 15–50% decrease in growth in presence of SEA depending on the concentration used. These findings may provide a rationale for designing nonpeptide inhibitors of PCs based on androgholide molecule present in abundance in the medicinally active plant Andrographis paniculata (AP)
Andrographolide, a diterpene lactone isolated from N. paniculata was studied for its antiinflammatory activity in different models of inflammation in rats after oral administration at doses of 30, 100 and 300 mg/kg. It significantly inhibited carrageenin-, kaolin- and nystatin-induced paw oedema. Moreover, andrographolide significantly inhibited the weight of granuloma induced by cotton pellet and decreased oedema in adjuvant-induced arthritis. Andrographolide, at 300 mg/kg, also inhibited dye leakage in acetic acid-induced vascular permeability. It was devoid of ulcerogenic effect on the stomach of rat in acute and chronic tests.
A number of new transformation products of andrographolide and of its acid transformation product, isoandrographolide, have been prepared; the structure of isoandrographolide has been elucidated. The chemical results described afford proof of the stereochemistry at C-3 and C-9 of the bicyclic nucleus of andrographolide; the assigned configuration of the substituents at C-4 is supported by an NMR study.
In a randomized placebo-controlled double blind study, the possible preventive effect against common colds of Kan Jang tablets made from Andrographis paniculata (Barm. F.) (Nees) dried extract was tudied during the winter season. The study was carried in a rural school. The students were divided in two groups, of which Group 1 (n=54), received 2 tablets of Kan Jang per day and Group 2 (n=53), 2 tablets of a placebo (P) per day during three months. The individuals were evaluated weekly by a clinician who diagnosed the presence or absence of common colds during the three months. The analysis of the occurrence of colds revealed that the administration of Kan Jang after the first month did not produced any significant difference. However, after the third month of intake of Kan Jang there was a significant decrease in the incidence of colds as compared to the placebo group. The rate of incidence of colds among the students treated with Kan Jang was 30% (16/54) compared to 62% (33/53). The relative risk of catching a cold was therefore 2.1 (1.32-3.33, 95% confidence interval) times lower for the Kan Jang group. The attributable protective effect of Kan Jang was 33%. The results suggest that Kan Jang tablets have a preventive effect against common colds during the winter period.
Kanjang(®) tablets (standardized Andrographis paniculata extract) have proven effective in the initial treatment of commond cold and sinusitis. Kanjang(®) tablets is a herbal formula, which has been developed by the Swedish Herbal Institute in Gothenburg. The tablets have shown a beneficial effect with regards to the subjective experience of initial symptoms of common cold and uncomplicated sinusitis, as well as to the duration of the symptoms. The preparation has been used in the Nordic countries for more than 12 years, mainly for reducing symptoms of common cold and sinusitis, and shortening the duration of the symptoms. In this controlled, double-blind study performed as a pilot trial at the Health Center, Hallehälsan, during the autumn of 1992, conducted in 50 patients, both subjective symptoms as well as duration of the symptoms were significantly reduced. From the results evaluated it is quite clear that Kanjang(®) tablets decrease the subjective symptoms of common cold as well as shortening of the period of sick leave significantly.
In a placebo-controlled double-blind study, the therapeutic effect of Kan Jang tablets made from Andrographis paniculata (Barm. F.) (Ness) dried extract was tested in patients with common colds. The patients were divided in two groups, in which group 1 (n = 33) received 1200 mg of Andrographis paniculata and group 2 (n = 28) a placebo (P).
On day 3–4 after treatment the possible effect of Kan Jang tablets on selected symptoms and clinical signs of common cold was evaluated. A significant reduction in clinical symptoms at day 4 of administration of the Kan Jang tablets was observed. A better efficacy against the placebo is discussed.
The differences in the total ‘sumscores’ of clinical and symptomatic findings indicate that the Kan Jang treated group did far better than the placebo group. We conclude that Kan Jang in a dose of 1200 mg daily has the capacity to significantly shorten the course/duration of the disease and therefore is indicated for an enhanced resistance to common colds.
One hour after the development of myocardial infarction by formation of thrombus, watery extract of Andrographis paniculata
Nees (APN) was injected intravenously to 7 dogs for observing the protective effect of this drug on ischemic myocardium. 6
dogs served as control group. In the treated group PGI2 increased remarkably, synthesis of TXA2 was inhibited, cAMP in platelets was elevated, CK-MB peak was lowered and appeared earlier, ELT was shortened, release of
platelet ß-GT was decreased, platelet maximum aggregation rate was inhibited, the size of ischemie area recorded by epicardial
ECG was reduced, the amplitude of ST segment elevation was lower than that in the control group, Q wave appeared in only one
dog. Pathologically, the myocardial structure surrounding the initially appearing ischemie area, i.e., the reversiblely damaged
area, became relatively normal, while the degree of myocardial degeneration and necrosis in the central part of the ischemie
area was mild. These data suggest that APN may limit the expansion of ischemie focus, exert marked protective effect on reversibly
ischemie myocardium and demonstrate a weak fibrinolytic action.
The aim of this experiment is to study the mechanism of APN in alleviating the Ca2+-overloading in dog model during the process of ischemic reperfusion. In comparison with the sustained ischemic group, the
parameters in the ischemic reperfusion group demonstrated: Ca2+ of ischemie region of myocardial cell increased (P<0. 05). Na+ increased remarkablyP<0. 01), the activity of Ca2+-ATPase dropped remarkably (P<0. 01),and MDA increased significantly (P<0. 01). Whereas in the group pretreated with APN, the Ca2+ in the relevant area reduced (P<0. 05), Na+ decreased significantly (P<0. 01), the activity of Ca2+-ATPase and Na+-K+ ATPase increased remarkably (P<0. 01), and MDA decreased significantly (P<0. 01). These findings indicate that APN may improve the activity of sarcolemma ATPase in alleviating the Ca2+ and Na+-overloading by decreasing the harmful effect of oxygen free radicals.
In experimental dogs, the effect of APN in alleviating the ischemiareperfusion injury was prominent. Compared with the sustained
ischemia group, superoxide dismutase (SOD) in the ischemic region of myocardial tissue in the ischemiareperfusion group was
significantly decreased and malondialdehyde (MDA) markedly increased: Ca2+ in myocardial cells was increased; and ultrastructural changes of myocardial tissues were severe. In the APN-pretreated ischemia-reperfusion
group, on the contrary, all the above parameters showed reversely, i,e., SOD increased, MDA and intracellular Ca2+ decreased, the ultrastructure changes were less distorted.
This paper presents the standard procedure for isolating lymphocytes and granulocytes from blood, using the Isopaque-Ficoll technique. A procedure for isolating granulocytes and macrophages from peritoneal fluid is also described.
Dehydroandrographolide succinic acid monoester (DASM) is the dehydroandrographolyl ester of succinic acid; and andrographolide, from which DASM is made, is the major diterpenoid lactone found in the Chinese medicinal herb, Andrographis paniculata. DASM has been found to be an inhibitor against the human immunodeficiency virus (HIV) in vitro. It was nontoxic to the H9 cell at the concentrations of 50-200 (average, 108) micrograms/ml and was inhibitory to the HIV-1 (IIIB) at the minimal concentration of 1.6-3.1 (average 2.0) micrograms/ml. It was also inhibitory to two other strains of HIV-1 and a strain of HIV-2. This inhibitory effect could also be demonstrated in cultures of activated human blood mononuclear cells; the 50% toxic dose and the 50% HIV inhibitory dose were about 200-greater than or equal to 400 and 0.8-2 micrograms/ml, respectively. At the subtoxic concentration, DASM partially interfered with HIV-induced cell fusion and with the binding of HIV to the H9 cell. Presumably, it also interfered with HIV replication at another unidentified step(s).
One hundred and fifty-two adult patients with pharyngotonsillitis were enrolled in the randomized double blind study to assess the efficacy of Andrographis paniculata. The patients were randomized to receive either paracetamol or 3 g/day of Andrographis paniculata or 6 g/day of Andrographis paniculata for 7 days. The baseline characteristics of the patients among the three groups were not different. The efficacy of paracetamol or high dose Andrographis paniculata was significantly more than that of low dose Andrographis paniculata at day 3 in terms of the relief of fever and sore throat. The clinical effects were not different at day 7. Minimal and self limiting side effects were found in about 20 per cent in each group.
In 16 dogs the endothelium of the left anterior descending coronary artery was injured mechanically. Then a copper wire was inserted into the lumen as a choke of flow and the vessel was slightly compressed from outside by a constrictor. Eight dogs had been treated beforehand with a preparation of flavone extracted from the root of the Chinese medicinal herb Andrographis paniculata (TFAP). In the control group, saline solution was given, the epicardially recorded ST segment started to elevate within 15 minutes, the platelet aggregation rate and the plasma levels of TXB2 increased rapidly, whereas the level of 6-k-PGF1 alpha remained stable. Platelet cGMP rose continuously; however, platelet cAMP rose only at 60 minutes. Histological findings confirmed the occurrence of arterial thrombus and myocardial necrosis. Contrariwise, in the pretreated group there was no elevation of the ST segment, plasma 6-k-PGF1 alpha and platelet cAMP were increased, the production of TXB2 and aggregation of platelets were inhibited, and no thrombus or myocardial infarction was induced. All data suggest that TFAP might promote the synthesis of PGI2, inhibit the production of TXA2, stimulate the synthesis of cAMP in platelets, impede aggregation of platelets, and thereby prevent the formation of thrombi as well as the development of myocardial infarction.
One hour after the development of myocardial infarction by formation of thrombus, watery extract of Andrographis paniculata Nees (APN) was injected intravenously to 7 dogs for observing the protective effect of this drug on ischemic myocardium, 6 dogs served as control group. In the treated group PGI2 increased remarkably, synthesis of TXA2 was inhibited, cAMP in platelets was elevated, CK-MB peak was lowered and appeared earlier, ELT was shortened, release of platelet beta-GT was decreased, platelet maximum aggregation rate was inhibited, the size of ischemic area recorded by epicardial ECG was reduced, the amplitude of ST segment elevation was lower than that in the control group, Q wave appeared in only one dog. Pathologically, the myocardial structure surrounding the initially appearing ischemic area, i.e, the reversibly damaged area, became relatively normal, while the degree of myocardial degeneration and necrosis in the central part of the ischemic area was mild. These data suggest that APN may limit the expansion of ischemic focus, exert marked protective effect on reversibly ischemic myocardium and demonstrate a weak fibrinolytic action.
Picroliv (active principle from Picrorrhiza kurroa), its major components picroside I, catalpol, kutkoside I, kutkoside, andrographolide (active constituent of Andrographis paniculata), silymarin and Phyllanthus niruri extract were tested for the presence of anti hepatitis B virus surface antigen (anti HBs) like activity. HBsAg positive serum samples obtained from hepatitis B virus (HBV) associated acute and chronic liver diseases and healthy HBsAg carriers were used to evaluate the anti-HBs like activity of compounds/extract. The latter were mixed with serum samples and incubated at 37 degrees C overnight followed by HBsAg screening in the Elisa system. A promising anti-HBsAg like activity was noted in picroliv (and its major components) catalpol, P. niruri which differed from the classical viral neutralization. Picroliv also inhibited purified HBV antigens (HBsAg and HBsAg) prepared from healthy HBsAg carriers. The in vitro testing system appears to be a suitable model to identify an agent active against HBV, prior to undertaking detailed studies.
In experimental dogs, the effect of APN in alleviating the ischemia-reperfusion injury was prominent. Compared with the sustained ischemia group, superoxide dismutase (SOD) in the ischemic region of myocardial tissue in the ischemia-reperfusion group was significantly decreased and malondialdehyde (MDA) markedly increased: Ca2+ in myocardial cells was increased; and ultrastructural changes of myocardial tissues were severe. In the APN-pretreated ischemia-reperfusion group, on the contrary, all the above parameters showed reversely, i.e., SOD increased, MDA and intracellular Ca2+ decreased, the ultrastructure changes were less distorted.
So far known Andrographis paniculata Nees (AP) is a hepatoprotective, antiplatelet and antithrombotic drug. In this experiment its hypoglycaemic effect has been tried in various way. Water extract of AP 10 mg/kg body weight can prevent induction of hyperglycaemia significantly (P < 0.001) induced by oral administration of glucose 2 mg/kg body weight. But any how failed to do so in adrenaline induced hyperglycaemia. It also failed to demonstrate any "fasting blood sugar lowering effect" upon chronic administration (6 weeks) of AP. So probably AP prevents glucose absorption from gut. Whole experiment was done on rabbits.
Restenosis rate after coronary angioplasty has been up to 30%-40%. To solve this problem, we studied the effects of Andrographis Paniculata Nees (APN) and fish oil (FO, omega 3 polyunsaturated fatty acids over 70%) on atherosclerotic stenosis and restenosis after experimental angioplasty and the relevant mechanisms of APN and FO. Preliminary results showed that APN can significantly alleviate atherosclerotic iliac artery stenosis induced by both deendothelialization and high cholesterol diet (HCD) and restenosis following angioplasty in rabbits. FO showed the same but milder effects than APN did. Both APN and FO significantly inhibited blood monocytes to secrete growth factors in vivo. Ca(++)-ATPase activity of cell membrane of atherosclerotic rabbits was significantly decreased, while APN or FO, especially the former alleviated this reduction. Refined extract of APN significantly decreased in vitro resting platelet [Ca++]i and in vivo the resting and thrombin-stimulated platelet [Ca++]i after oral administration of APN for 2 weeks. APN significantly inhibited cell growth or DNA synthesis in dose-dependent manner. In conclusion because of the mechanisms described above, APN can alleviate atherosclerotic artery stenosis induced by both deendothelialization and HCD as well as lower restenosis rate after experimental angioplasty. The effects of APN are evidently superior to those of FO.
63 patients of cardiac and cerebral vascular diseases were observed at 3 hours and/or one week after taking Andrographis paniculata (AP) extracts. Results showed that both 1 min. and 5 min. platelet aggregation induced by ADP were significantly inhibited (P < 0.001), 33 cases of them were observed for one week. The aggregation rate was even significantly lower than that of 3 hours. Serotonin (5-HT) release reaction from platelet was observed in 20 volunteers taking AP. Result showed 5-HT released from platelet decreased (P < 0.01), but plasma 5-HT level remained unchanged. The ultrastructural observation showed that AP could inhibit the releasing of dense and alpha agranules from platelet and dilating of canalicular system. It suggested that a raise of platelet cAMP level might be the mechanism of antiplatelet effect of AP.
EtOH extract and purified diterpene andrographolides of Andrographis paniculata (Acanthaceae) induced significant stimulation of antibody and delayed type hypersensitivity (DTH) response to sheep red blood cells (SRBC) in mice. The plant preparations also stimulated nonspecific immune response of the animals measured in terms of macrophage migration index (MMI) phagocytosis of 14C-leucine labelled Escherichia coli and proliferation of splenic lymphocytes. The stimulation of both antigen specific and nonspecific immune response was, however, of lower order with andrographolide than with the EtOH extract, suggesting thereby that substance(s) other than andrographolide present in the extract may also be contributing towards immunostimulation.
The aim of this experiment is to study the mechanism of APN in alleviating the Ca(2+)-overloading in dog model during the process of ischemic reperfusion. In comparison with the sustained ischemic group, the parameters in the ischemic reperfusion group demonstrated: Ca(2+) of ischemic region of myocardial cell increased (P < 0.05), Na+ increased remarkably (P < 0.01), the activity of Ca(2+)-ATPase dropped remarkably (P < 0.01), and MDA increased significantly (P < 0.01). Whereas in the group pretreated with APN, the Ca(2+) in the relevant area reduced (P < 0.05), Na+ decreased significantly (P < 0.01), the activity of Ca(2+)-ATPase and Na+-K+ ATPase increased remarkably (P < 0.01), and MDA decreased significantly (P < 0.01). These findings indicate tha APN may improve the activity of sarcolemma ATPase in alleviating the Ca(2+) and Na+ -overloading by decreasing the harmful effect of oxygen free radicals.
1. The hypotensive activity of an aqueous extract of Andrographis paniculata was studied using chronic intraperitoneal (i.p) infusions by osmotic pumps. The extract exhibited a dose-dependent hypotensive effect on the systolic blood presure (SBP) of spontaneously hypertensive rats (SHR).
2. The optimum hypotensive dose determined was repeated in a study in SHR and their normotensive controls, Wistar Kyoto (WKY) rats, to demonstrate its comparative effects on the SBP, plasma and lung angiotensin-converting enzyme (ACE) activities, as well as on lipid peroxidation in the kidneys, as measured by thiobarbituric acid (TBA) assay.
3. The extract significantly lowered the SBP of both SHR and WKY rats.
4. Plasma, but not lung, ACE activity and kidney TBA level were significantly lower in extract-treated SHR when compared with vehicle-treated SHR controls.
5. Plasma and lung ACE activities as well as kidney TBA levels were not significantly different between extract-and vehicle-treated WKY rats.
6. This study indicates that the aqueous extract of A. paniculata lowers SBP in the SHR possibly by reducing circulating ACE in the plasma as well as by reducing free radical levels in the kidneys. The mechanism(s) of hypotensive action seems to be different in WKY rats.
The cardiovascular activities of crude water extract (WE) of Andrographis paniculata (Burm. f.) Nees (Acanthaceae), its three semi-purified ethyl acetate (FA), n-butanol (FB) and aqueous (FC) fractions, as well as andrographolide, a major plant constituent, were elucidated in anaesthetized Sprague-Dawley (SD) rats for the very first time. FA and andrographolide, which possesses multiple pharmacological activities, elicited no drop in mean arterial blood pressure (MAP), while WE, FB and FC produced a significant fall in MAP in a dose-dependent manner without significant decrease in heart rate. The ED50 values for WE, FB and FC were 11.4, 5.0 and 8.6 mg/kg-respectively. These suggested that the hypotensive substance(s) of the crude water extract was concentrated in FB. Pharmacological antagonist studies were consequently only tested in FB (5 mg/kg). The hypotensive action of FB was not mediated through effects on the beta-adrenoceptor, muscarinic cholinergic receptor and angiotensin-converting enzyme, for it was not affected by propranolol, atropine and captapril, respectively. However, it seems to work via alpha-adrenoceptors, autonomic ganglion and histaminergic receptors, since the hypotensive effect of FB was negated or attenuated in the presence of phentolamine, hexamethonium as well as pyrilamine and cimetidine.
Andrographolide. Part 1
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- R Mehrotra
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A Double-blind study with a new mon odrug Kan Jang: Decrease of symptoms and improvements in the recovery from com-mon colds, Phytotherapy Res Anti-inflam-matory activity of and rograph olide
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Platelet-Ac-tivating Factors Andrographis paniculata (Burn.f.) Nees., In: Chinese Drugs of Plant Origin, Chemistry, Phar-macology and Use in Traditional and Modern Medicine
- R N Pinckard
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Controlled clinical study on the efficacy of Kan Jang Tablets in common cold – a pilot trial
- J Melchior
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Guelbenkian Research and Drug Quality Control Laboratories of the Drug Agency
- A Panossian
A. Panossian, Guelbenkian Research and Drug Quality
Control Laboratories of the Drug Agency, 49/4 Komitas str., 375051, Armenia
Platelet-Activating Factors In: Inflammation. Basic principles and clinical correlates
- R N Pinckard
- J C Ludwig
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Hypoglycemic effects of Andrographis paniculata Nees on non-diabetic rabbits
- D Bensky
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Bensky, D., Gamble, A. (eds): Chinese Herbal Medicine Materia Medica, revised edition, Eastland Press, p. 95, 1993.
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BN 52021 and related compounds: a new series if Highly specific PAF Acether antagonists isolated from Ginkgo biloba L., Blood Vessel
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