Molecular docking analysis to validate the efficacy of traditional Siddha polyherbal Formulation Aavarai Bhavanai Chooranam(ABC)against enzyme alpha-glucosidase for Type II Diabetes Mellitus

Background:The Siddha system of traditional medicine has historically been utilized to treat a wide range of illnesses,including noncommunicable diseases.With more than 62 million people in India already living with diabetes,the disease is quickly gaining the status of a possible epidemic.It has been demonstrated that this medical theory contains anti-diabetic substances.The goal of this work is to assess in silico computational investigations of the phytoconstituents in the traditional Siddha polyherbal preparation ABC,which is frequently used to treat diabetes.Method:Alpha-Glucosidase was used as the target enzyme in docking calculations for recovered phytocomponents.With the help of Auto Dock tools,necessary hydrogen atoms,Kollman unified atom type charges,and solvation parameters were added.The Lamarckian genetic algorithm and the Solis and Wets local search approach were used to simulate docking.Results:A total of 13 bioactive lead compounds were identified from the Siddha Formulation ABC.According to the herb’s stated data,the target enzyme Alpha-Glucosidase can interact with the phytochemicals Beta-Sitosterol,Amyrin,Lupeol,Arjunic acid,Arjungenin,Tinosporide,and Tembetarine up to four or five times.The second-placed substances,which had a maximum of two to three interactions with the target enzyme Alpha-Glucosidase,were betulonic acid,kaempferol,gallic acid,and barbaloin.Conclusion:The implementation of these formulations in future preclinical and clinical studies could result in the effective management of Type II Diabetes Mellitus.

Antiplasmodial activity of traditional polyherbal remedy from Odisha, India:Their potential for prophylactic use

Objective:To evaluate the potential prophylactic activity of traditional polyherbal remedy against malaria.Methods:A traditional polyherbal remedy against malaria from Odisha,India was evaluated for its potential prophylactic activity using in vitro hepatic cell lines assay and the murine malaria system Plasmodium yoelii yoelii/Anopheles stephensi.Results:The polyherbal extract inhibited the Plasmodium yoelii hepatic stages in vitro(IC500.74 mg/m L),a therapeutic index of 9.54.In mice treated with the aqueous extract(2 000 mg/kg/day),peak parasitaemia values were 81%lower in the experimental2.35%±0.14%as compared to controls 12.62%±0.52%(P<0.001),suggesting significant prophylactic activity.Conclusions:The observations provide a proof of concept for a traditional malaria prophylactic remedy used by tribal populations in India.

Safety evaluation of a polyherbal formulation containing hydroalcoholic extracts of Hippophae salicifolia, Nyctanthes arbor-tristis, Ocimum tenuiflorum, and Reinwardtia indica in rodents

Dear Editor, Herbal medicines have been used for prevention and treatment of human diseases and promotion of healthy living. These medicines, often self medicated and consumed as concentrated extracts, are not strictly regulated. Considering their popular use and increasing safety concerns, thorough evaluations of their efficacy and safety are warranted to protect consumers from potential adverse effects. Toxicity tests （acute, sub- acute and chronic） using animals are widely applied to evaulate adverse effects of a drug and thereby determine its ＂No Observed Adverse Effect Level＂ （NOAEL）.

Mutagenic Potential of Medicinal Polyherbal Preparations

Extracts of twelve medicinal polyherbal preparations in powder form sold at retail shops were tested for mutagenicity using Ames in vitro test. Five of the polyherbal preparations were found to be mutagenic (p ≤ 0.05) at 250 μg/ml. Two mutagenic preparations comprised of traditionally used medicinal plants with no mutagenicity property being reported. However, one polyherbal preparation which contained one mutagenic plant was found not mutagenic. Under the conditions of this study, it can be concluded that some polyherbal preparations were potentially mutagenic and mutagenicity of polyherbal preparation cannot always be deduced from the mutagenicity status of each individual plant components of the polyherbal preparations.

“Diabegon”, a safe and effective polyherbal therapy for type 2 diabetes mellitus

AIM: To investigate the antihyperglycemic, antihyperlipidemic and antioxidant functions of a polyherbal formulation, "Diabegon", in human subjects with type 2 diabetes mellitus.METHODS: A total of 33 human subjects with type 2 diabetes mellitus were recruited for the study and all anthropological and biochemical parameters were recorded at the time of registration. The subjects were given hot water extract obtained from 10 gm of "Diabegon" powder, "Diabegon kwath", on an empty stomach everyday in the morning under personal supervision for 6 mo. The therapeutic functions of the "Diabegon kwath" was assessed by monitoring the blood glucoselevels at monthly intervals and glycosylated hemoglobin, lipid profile and biomarkers of oxidative stress, liver and kidney function markers at three monthly intervals in the study subjects. RESULTS: Daily administration of hot water extract of "Diabegon" regularly for 6 mo resulted in significant reductions of blood glucose and glycosylated hemoglobin levels. There was also a significant increase in high density lipoprotein cholesterol levels with concomitant decreases in total cholesterol, triglycerides, low density lipoprotein cholesterol and very low density lipoprotein. A significant improvement in glycosuria and proteinuria was also observed. Also, the subjects exhibited a significant improvement in enzymatic and nonenzymatic biochemical markers of oxidative stress. The kidney and liver functions remained normal and in fact improved in many subjects.CONCLUSION: The study which is first of its kind, advocates "Diabegon kwath" as a safe and effective Ayurvedic therapy for the treatment of human type 2 diabetes mellitus and further placebo controlled trial may substantiate the therapeutic efficacy of the formulation.

Evaluation of Acute and Repeated Dose Toxicity of the Polyherbal Formulation Linkus Syrup in Experimental Animals

The objective of the present study was to evaluate the pre-clinical efficacy and toxicity of polyherbal cough syrup Linkus. Method: Animals (healthy Wistar albino rats;(150 - 250 g) of either sex) were housed under standard environmental conditions;i.e. 25°C ± 1°C and 12 h dark/light cycle. Food and water were available at libitum. The rats were treated orally with the recommended doses of the test drug (Linkus). After 15 minutes, they were individually placed in a closed Plexiglas chamber (20 × 10 × 10 cm) and exposed to citric acid (0.1 g/ml) inhalation for 7 minutes. The cough reflexes were produced and counted for the last 5 minutes and compared with those of the control animals. The following studies were conducted to evaluate the toxicity of the test drug in healthy Wistar albino rats: lethal dose50 (LD50);rats of either sex (n = 10/sex) were treated orally with doses (1 or 5 g/kg) of the test drug. Mortality and behavioral changes were observed for 1 week. Repeated dose toxicity on the healthy Wistar albino rats of both sexes (n = 5/dose/sex) was treated orally with doses of 20 mg/kg (adult human dose = ~1400 mg), 500 mg/kg (adult human dose = ~35,000 mg) and 1000 mg/kg (adult human dose = ~70,000 mg) of test drug (Linkus) for 14 days. Additionally, the control animals were treated orally with water for 14 days. Results: In female rats, the test drug (Linkus) at the dose of 300 mg/kg caused significant (p < 0.01) reduction in the cough reflexes as compared to the control. However, in male rats, a significant reduction was observed at the tested dose of 200 mg/kg (p < 0.05) and 300 mg/kg (p < 0.01). The test product did not cause mortality in rats at the given doses of 1 or 5 g/kg. Other signs of toxicity like hair loss and weight reduction were not observed. In female and male rats, the test drug (Linkus) at different doses did not show any abnormal effects on complete blood count profile of rats. Serum enzyme markers, i.e. alanine aminotransferase (ALT), alakaline phosphatase, gamma glutamyle transferase (GGT), direct bilirubin, creatinine, and proteins were also observed and found that the test drug at a higher dose did not cause any of the abnormality and had shown significant p value as compared to the control. Conclusion: The test drug (Linkus) could be an effective and safe cough syrup because it did not show any of the side effects or toxicity on experimental animals.

Jatonik polyherbal mixture induced rat liver MMPT pore opening in normal Wistar rat:In vitro and in vivo studies

Objective:To assess acute toxicity,the in vitro and in vivo effects of methanol and ethyl acetate extracts(JME and JEE)of Jatonik polyherbal mixture on some mitochondria-related parameters and their effect on the activity of some liver enzymes.Methods:Acute toxicity of JME and JEE was determined using Lorke’s method.In vitro and in vivo opening of the mitochondrial membrane permeability transition pore(MMPT pore)was spectrophotometrically assayed.Production of malondialdehyde(MDA)as an index of lipid peroxidation and the activity of mitochondrial ATPase was evaluated in vitro and in vivo and the effect of JME and JEE on the activity of liver enzymes such as alkaline phosphatase(ALP),aspartate and alanine aminotransferase(AST and ALT)and gamma-glutamyl transferase(GGT)was also investigated.Results:JME had an LD_(50) of 3808 mg/kg b.w whereas JEE had an LD_(50) greater than 5000 mg/kg b.w.of rats.After the rats have been fed with both extracts,a photomicrograph of a piece of liver tissue showed no apparent symptoms of toxicity.From the in vitro and in vivo studies,both extracts prompted intact mitochondria to open their MMPT pores.When compared to the control,lipid peroxide product release and ATPase activity were significantly increased(P<0.05)in vitro and in vivo.The activities of AST,ALT,and GGT were all reduced at 50 mg/kg when treated with JME,but the activity of AST was considerably enhanced when treated with JEE(P<0.05).The results revealed that both JME and JEE of the Jatonik polyherbal mixture had low toxicity,profound MMPTpore induction,and enhanced ATPase activity,but an increased MDA production.Conclusion:Jatonik extracts may be a promising target for drug development in diseases where there is dysregulation of apoptosis,however,further studies are needed to better clarify the molecular mechanism involved in these phenomena.

A novel herbal combination ameliorates ovarian dysfunction and regulates altered biochemical parameters in rats with letrozole-induced polycystic ovary syndrome

Objective:To investigate the potential activity of novel herbal combination and novel herbal formulation(syrup)in female Sprague Dawley rats with letrozole-induced polycystic ovary syndrome(PCOS).Methods:Forty-two rats were randomly divided into seven groups with six rats in each group.Group 1 received 0.5%carboxy methylcellulose orally for 37 days and served as the normal control group.Group 2 was orally administered with letrozole of 1 mg/kg for 21 days and served as the PCOS induction group without treatment.Group 3 to 7 were administered with letrozole of 1 mg/kg for 21 days orally to induce PCOS,and then respectively received clomiphene citrate at 1 mg/kg,100 and 200 mg/kg of novel herbal combination,200 mg/kg of novel herbal formulation(syrup),and 400 mg/kg of marketed formulation of Pushyanuga churna,once daily for 15 days.Effects of the novel herbal combination and its syrup formulation were evaluated on the hormonal profile,the levels of antioxidants,the lipid profile and on the ovarian morphology,using letrozole-induced PCOS model in rats.Results:Letrozole caused alterations in hormonal levels and lipid levels similar to PCOS and ovarian histology showed presence of ovarian cysts confirming the induction of PCOS in rats.On treatment with the novel herbal combination and its syrup formulation in PCOS-induced rats,the altered hormonal and lipid profiles showed significant recovery to normal levels.Ovarian histology confirmed the restoration of folliculogenesis in the PCOS-induced rats.The treatment with the syrup formulation of novel herbal combination was found to be more effective than novel herbal combination and showed better recovery in various parameters evaluated.The results of the study,however,suggested that treatment with novel herbal combination and its syrup formulation provided minimal protection against oxidative stress caused due to the induction of PCOS.Conclusions:The integrated approach for management of PCOS is to counterbalance the limitations associated with modern therapy.Both the novel herbal combination and the syrup formulation of novel herbal combination show efficacy in the management of PCOS in rats and restore folliculogenesis in the ovary.The syrup formulation of novel herbal combination is most effective in the management of PCOS and shows potential to be developed as an adjuvant therapeutic agent.

Evaluation of the Anti-Diabetic Potential of the Methanol Extracts of <i>Aloe camperi</i>, <i>Meriandra dianthera</i>and a Polyherb

The objective of the study was to evaluate the anti-diabetic activities of methanol extracts of Aloe camperi (AC), Meriandra dianthera (MD) and a polyherbal drug (PH) in diabetes induced Wistar albino rats. A single dose of alloxan monohydrate (150 mg/kg, i.p.) was used to induce diabetes mellitus (DM). Diabetes was confirmed by the elevated blood glucose levels determined after 72 h of induction. Animals with mean fasting blood glucose (FBG) level more than 200 mg/dl were recruited for the experiment. The herbal extracts at doses of 200 and 400 mg/kg and standard drugmetformin (5 mg/kg) were administered orally to the diabetic rats for 21 days and the FBG level was estimated on 0, 7, 14 and 21 days. The herbal extracts showed dose-dependent fall in FBG levels and the result exhibited very significant (P < 0.001) decreases in FBG level by the end of the experimental day as compared to the diabetic control. The highest antihyperglycemic effect was observed by MD extract at 400 mg/kg and was comparable to the standard drug. Oral glucose tolerance test (OGTT) was also conducted on normal rats and thus glucose at 2 g/kg per body weight was loaded via oral gavage to all groups 30 min after extract administration. All the groups showed significant increase (P P The hyperglycemia with glucose challenge was significantly brought down (P < 0.001) by all herbal extracts at 60 and 120 min relative to the negative control. Moreover, acute oral toxicity tests was conducted based on the protocols of OECD-425 and thus the LD50 of the herbal extracts was estimated to be greater than 2000 mg/kg. Statistical analysis was performed using One-Way ANOVA followed by Dunnett’s test for multiple comparisons, and values of P < 0.05 were considered as statistically significant.

Identification of Blood Serum Lipid Compositions Isolated from Diabetic PatientsmType II Treated with Polyherbs by Capillary Gas.Chromatography

This study included treatment of diabetic patients--type II with a polyherbs containing Nigella sativa, Trigonell foenum-graceum, Cyperus rotundus, Teucrium polium divided into two groups, first group was taken herbs with chemical treatment （drugs） and the other group which used herbs only. These groups were compared with healthy persons as a control group. Separation of the lipid component containing in the serum of two groups under study for diabetes mellitus patient--type lI before and after treatment with polyherbs by patients were performed. The separation of the components of different kinds of lipid parts like cholesterol ester （CE）, triglyceride and phospholipids, in the blood using thin layer chromatography （TLC） and capillary gas chromatography （CGC）. The results of this study for ester cholesterol part of serum patients show that there was a significant increase in the percentage of saturated fatty acid （SFA） and monounsaturated fatty acid （MUFA） before the treatment of the two groups compared to the control group and a significant decrease was observed in the percentage of these fatty acid after the treatment by polyherbal mixture than the percentage before treatment. Also, the results for the same part of ester cholesterol serum were showed a significant decrease in percentage of polyunsaturated fatty acid （PUFA） in the two groups of diabetes mellitus patients in comparison with the control group and there were a significant increase observed in PUFA percentage after the treatment. For triglyceride part in serum lipid, the results of this study were shown that there was a significant increase in percentage of SFA and PUFA before treatment in comparison with control group and after treatment for three months of the two groups of patients, shows a significant decrease in SFA but an increase in the percentage of PUFA was observed than that observed before treatment, also, there was a significant decrease in MUFA before treatment comparison with control group, while there was a significant increase which was observed after treatment in a percentage for the two groups of triglyceride part in serum lipid. The results indicated that there was a significant decrease in percentage of SFA before and after also in MUFA after the treatment in both groups compared with control and a significantly increase in PUFA percentage was also shown for phospholipids part in the serum.

An in vitro Anti-urolithiasis Activity of a Herbal Formulation:Spinacia oleracea L.and Coriandrum sativum L.

Background:Hard mineral and acid salt deposits that clump together in concentrated urine are known as kidney stones.A complicated chain of physicochemical events,including hyper saturation,nucleation,growth,aggrega-tion,and retention in the urinary tract,leads to urolithiasis,the third most prevalent urinary tract issue.Numerous traditional medications and therapies are less successful in treating urolithiasis and frequently cause recurrences.Objective:The present study is focused on evaluating the anti-urolithiasis activities of the polyherbal formulation prepared from Spinacia oleracea L.and Coriandrum sativum L.seeds.Methods:To evaluating the anti-urolithiasis activities of the polyherbal formulation prepared from S.oleracea and C.sativum seeds against oxalate crystals by employing an in vitro inhibition,aggregation,and nucleation assay,employing a spectrophotometer followed by microscopic observation,and further monitored by egg semiperme-able membrane model,using cystone as a standard drug.Results:In the present work,the alkaloids,glycosides,flavonoids,glycosides,phenols,saponins,steroids,tannins,terpenoids,and triterpenoids were found in the extracts of S.oleracea and C.sativum.The in vitro assays in the present study clearly indicated that all the mixture extracts readily prevented crystal nucleation,growth and ag-gregation.The aqueous extract of the mixture inhibited significant inhibitory potential against the crystallization process.Conclusion:It can be said that the phyto-constituents enriched homemade preparation possibly will be used as a medication for the management of kidney stones by dissolving the oxalate stone in the kidney.

复方草药制剂减轻高草酸尿导致的氧化应激及预防草酸钙沉积和大鼠肾细胞损伤(英文)

INTRODUCTION:Cystone is an approved Ayurvedic polyherbal proprietary medicine used in India for various urinary disorders,including urolithiasis.AIM:To evaluate the protective effect of Cystone against hyperoxaluria-induced oxidative stress and calcium oxalate crystal deposition in urolithiasis.METHODS:Ethylene glycol(EG)(0.75%,V/V)in drinking water was given to rats for 28 days to induce urolithiasis with simultaneous treatment of Cystone(500 and 750 mg/kg body weight),and various urinary risk factors of urolithiasis and antioxidant markers were assessed.RESULTS:EG treatment lead to increased urine volume and lowered urinary pH,along with increased urinary excretion of oxalate,calcium and phosphate in untreated animals.These changes caused extensive calcium oxalate crystal deposition,increased lipid peroxidation and decreased activity of antioxidant enzymes(SOD,catalase and GPx)in the kidney of untreated rats.Cystone prevented these hyperoxaluric manifestations and inhibited calcium oxalate crystal deposition in treated rats at both doses.CONCLUSIONS:Cystone therapy provides protection against hyperoxaluria-induced oxidative stress and calcium oxalate crystal deposition by improving renal tissue antioxidant status and diuresis.

Status of Indian medicinal plants in the International Union for Conservation of Nature and the future of Ayurvedic drugs: Shouldn’t think about Ayurvedic fundamentals?

The present market for herbal drugs is estimated about ?40 billion, which is expected to increase by 16% in next 3-4 years. The current production of many Ayurvedic herbs is less than their market demand, which incentivizes adulteration in the Ayurvedic drug supply chain. The present work aims to highlight the most used Ayurvedic plants that have been listed in the International Union for Conservation of Nature's "red list" of endangered or vulnerable plants. The future of Ayurvedic medicines from these listed plants is uncertain, as the collection of herbs from their natural habitat is prohibited and their cultivation does not meet market demands. Many of these plants, such as Taxus baccata and T. wallichiana, are endangered and are only grown in their natural habitats;their cultivation in other areas is impractical. This is the present state, and will worsen as demand continues to grow, with increasing populations and increasing adoption of this system of medicine. It is possible that in coming years most of the Ayurvedic drugs will be adulterated, and will cause only side effects rather than the therapeutic effects. The Ayurvedic fundamentals are under-explored areas where the Ayurvedic practitioners and research scientists can work together. The scientific work on the basic principles will unravel many unknown or little-known facts of this ancient science. Hence, the present review emphasizes the conservation of Ayurvedic herbs, minimization of the use of medicinal plants and the promotion of the research based on Ayurvedic fundamentals.

源自印度药用植物的一种抗溃疡复方制剂(英文)

AIM: The present study was aimed at evaluating the antiulcer activity of the polyherbal formulation (PHF) containing the leaf extracts of Moringa oleifera, Raphinus sativus, and Amaranthus tricolor in rats. METHODS: The antiulcer activity of the polyherbal formulation (PHF) was evaluated using different models of gastric ulcers: ethanol-induced, indomethacin-induced and ischemia reperfusion-induced gastric ulcers. Efficacy was assessed by determining the ulcer index. RESULTS: Administration of the polyherbal formulation (150mg·kg-1 , p.o.) offered significant protection against indomethacin-induced, ethanol-induced, and ischemic reperfusion-induced ulcer models when compared to the control group. CONCLUSION: PHF, containing leaf extracts of Moringa oleifera, Raphinus sativus, and Amaranthus tricolor, was found to possess antiulcer properties in three experimental animal models of gastric ulcers, and these findings suggest that the significant gastroprotective activity could be mediated by its antioxidant activity.