Rosmarinic acid and its derivative's duel as antitubercular agents: insights from computational prediction to functional response in vitro.

Tuberculosis is one of the most dreadful infectious diseases, afflicting global populations with anguish. With the emergence of multi-drug resistant strains of mycobacteria, the imperative for new anti-tuberculosis drugs has grown exponentially. Thus, the current study delves into evaluating the impact of Perovskia abrotanoides and its active metabolites-namely, rosmarinic acid and its derivatives-against strains of Mycobacterium tuberculosis (Mtb). Through the use of the CRI assay, the antimycobacterial potential of the high-altitude medicinal plant P. abrotanoides was gauged, while docking and molecular dynamics simulations unveiled plausible targets. Of these, the peak antimycobacterial effectiveness was observed in the P. abrotanoides ethyl acetate extract with 125 µg/mL as minimum inhibitory concentration against various strains of M. tuberculosis, encompassing H37Rv and strains resistant to multiple drugs. Following bioassay-guided fractionation and isolation, rosmarinic acid and rosmarinic acid methyl ester emerged as potent molecules against H37Rv and multidrug-resistant M. tuberculosis strains; minimum inhibitory concentration ranging from 15 to 32 µg/mL. Additionally, out of 22 targets explored, Mtb lipoamide dehydrogenase (PDB: 3II4) and Rv2623 (PDB: 3CIS) were forecasted as potential Mtb targets for rosmarinic acid and rosmarinic acid methyl ester, respectively, a supposition further affirmed by molecular simulations (100 ns). The stability of both complexes throughout the simulation was measured by protein backbone root-mean-square deviation, substantiating their roles as respective targets for antimycobacterial activities.Communicated by Ramaswamy H. Sarma.

Network pharmacology and molecular modelling study of Enhydra fluctuans for the prediction of the molecular mechanisms involved in the amelioration of nephrolithiasis.

In view of the ethno medicinal use of Enhydra fluctuans for the treatment of kidney stones; the present study aimed to elucidate the molecular mechanisms involved in the amelioration of nephrolithiasis through a network pharmacology approach. The phytoconstituents were queried in DIGEP-Pred to identify the regulated proteins. The modulated proteins were then enriched in the STRING to predict the protein-protein interactions and the probably regulated pathways were traced in the Kyoto Encyclopedia of Genes and Genomes. Further, the network was constructed using Cytoscape ver 3.5.1. Results showed that ß-carotene was found to be regulating maximum targets i.e. 26. In addition, 63 proteins were triggered by the components in which the vitamin D receptor was targeted by the maximum phytoconstituents i.e. 16. The enrichment analysis identified the regulation of 67 pathways in which fluid shear stress and atherosclerosis-associated pathways (KEGG entry hsa05418) regulated ten genes. Further, protein kinase C-α was traced in 23 different pathways. In addition, the majority of the regulated genes were identified from the extracellular space via the modulation of 43 genes. Also, nuclear receptor activity had the maximum molecular function via the regulation of 7 genes. Likewise, the response to organic substance was predicted to trigger the top genes i.e. 43. In contrast, Stigmasterol, Baicalein-7-o-glucoside, and Kauran-16-ol were found to have a high affinity to bind with the VDR receptor confirmed by the molecular modelling and the dynamics. Hence, the study elucidated the probable molecular mechanisms of E. fluctuans in managing nephrolithiasis and identified the lead molecules, their targets, and possible pathways.Communicated by Ramaswamy H. Sarma.

The Abundant Phytocannabinoids in Rheumatoid Arthritis: Therapeutic Targets and Molecular Processes Identified Using Integrated Bioinformatics and Network Pharmacology.

The endocannabinoid system consists of several phytocannabinoids, cannabinoid receptors, and enzymes that aid in numerous steps necessary to manifest any pharmacological activity. It is well known that the endocannabinoid system inhibits the pathogenesis of the inflammatory and autoimmune disease rheumatoid arthritis (RA). To the best of our knowledge, no research has been done that explains the network-pharmacology-based anti-rheumatic processes by focusing on the endocannabinoid system. Therefore, the purpose of this study is to further our understanding of the signaling pathways, associated proteins, and genes underlying RA based on the abundant natural endocannabinoids. The knowledge on how the phytocannabinoids in Cannabis sativa affect the endocannabinoid system was gathered from the literature. SwissTarget prediction and BindingDB databases were used to anticipate the targets for the phytocannabinoids. The genes related to RA were retrieved from the DisGeNET and GeneCards databases. Protein-protein interactions (high confidence > 0.7) were carried out with the aid of the string web server and displayed using Cytoscape. The Kyoto Encyclopedia of Genes and Genomes (KEGG) metabolic pathway analysis was used to perform enrichment analyses on the endocannabinoid-RA common targets. ShinyGO 0.76 was used to predict the biological processes listed in the Gene Ontology (GO) classification system. The binding affinity between the ligand and the receptors was precisely understood using molecular docking, induced-fit docking, and a molecular dynamics simulation. The network pharmacology analyses predicted that processes like response to oxygen-containing compounds and peptodyl-amino acid modification are related to the potential mechanisms of treatment for RA. These biological actions are coordinated by cancer, neuroactive ligand-receptor interaction, lipids and atherosclerosis, the calcium signaling pathway, and the Rap1 signaling pathway. According to the results of molecular docking, in the context of RA, phytocannabinoids may bind to important target proteins such PIK3CA, AKT1, MAPK9, PRKCD, BRAF, IGF1R, and NOS3. This entire study predicted the phytocannabinoids' systemic biological characteristics. Future experimental research is needed, however, to confirm the results so far.

Assessment of the systemic toxicity of Laghu vishagarbha taila, an Ayurvedic medicated oil formulation after dermal exposure.

Laghu vishagarbha taila (LVT) is a medicated oil preparation used in the Ayurvedic system of medicine and applied topically for the treatment of painful musculoskeletal and inflammatory disorders. It contains some mildly poisonous phytoconstituents which may show untoward effects upon application. The present study evaluated the toxicity of LVT in the acute, subacute, and subchronic dermal toxicity study in Wistar rats. LVT was tested for its compliance using physicochemical and analytical parameters as per standard methods prescribed in Ayurvedic Pharmacopoeia of India, while acute, subacute, and subchronic toxicity studies were carried out as per OECD 402, 410, and 411 guidelines, respectively. In the acute dermal toxicity study, a single dose of LVT (2000 mg/kg) was applied topically to rats, while in subacute and subchronic dermal toxicity study, the rats were topically applied LVT (1000 mg/kg) up to 28 and 90 days, respectively. LVT did not cause any alterations in clinical signs and no mortality or moribund stage was observed. The change in weekly body weight was insignificant compared with the vehicle control group. In subacute and subchronic dermal toxicity study, there were no significant changes in behavior, body weight, feed consumption, biochemical and hematological parameters, organ weight, and histological parameters compared with vehicle control rats. Topical application of single and repeated doses of LVT in rats did not exhibit adverse effects and suggests that the LD50 of LVT is more than 2000 mg/kg in the acute dose and NOAEL is more than 1000 mg/kg/day in repeated dose application.

Withanolides from Withania somnifera as an immunity booster and their therapeutic options against COVID-19.

Traditionally, Withania somnifera is widely used as an immune booster, anti-viral, and for multiple medicinal purposes. The present study investigated the withanolides as an immune booster and anti-viral agents against the coronavirus-19. Withanolides from Withania somnifera were retrieved from the open-source database, their targets were predicted using DIGEP-Pred, and the protein-protein interaction was evaluated. The drug-likeness score and intestinal absorptivity of each compound were also predicted. The network of compounds, proteins, and modulated pathways was constructed using Cytoscape, and docking was performed using autodock4.0, and selected protein-ligand complexes were subjected to 100 ns Molecular Dynamics simulations. The molecular dynamics trajectories were subjected to free energy calculation by the MM-GBSA method. Withanolide_Q was predicted to modulate the highest number of proteins, showed human intestinal absorption, and was predicted for the highest drug-likeness score. Similarly, combined network interaction identified Withanolide_Q to target the highest number of proteins; RAC1 was majorly targeted, and fluid shear stress and atherosclerosis associated pathway were chiefly regulated. Similarly, Withanolide_D and Withanolide_G were predicted to have a better binding affinity with PLpro, Withanolide_M with 3CLpro, and Withanolide_M with spike protein based on binding energy and number of hydrogen bond interactions. MD studies suggested Withanoside_I with the highest binding free energy (ΔGbind-31.56 kcal/mol) as the most promising inhibitor. Among multiple withanolides from W. somnifera, Withanolide_D, Withanolide_G, Withanolide_M, and Withanolide_Q were predicted as the lead hits based on drug-likeness score, modulated proteins, and docking score to boost the immune system and inhibit the COVID-19 infection, which could primarily act against COVID-19. HighlightsWithanolides are immunity boosters.Withanolides are a group of bio-actives with potential anti-viral properties.Withanolide_G, Withanolide_I, and Withanolide_M from Withania somnifera showed the highest binding affinity with PLpro, 3CLpro, and spike protein, respectively.Withanolides from Withania somnifera holds promising anti-viral efficacy against COVID-19.Communicated by Vsevolod Makeev.

Network pharmacology of AYUSH recommended immune-boosting medicinal plants against COVID-19.

The Ministry of AYUSH recommended the use of a decoction of the mixture of Ocimum tenuiflorum, Cinnamomum verum, Piper nigrum, Zingiber officinale, and Vitis vinifera as a preventive measure by boosting the immunity against the severity of infection caused by a novel coronavirus (COVID-19). The present study aimed to identify the probable modulated pathways by the combined action of AYUSH recommended herbal tea and golden milk formulation as an immune booster against COVID-19. Reported phytoconstituents of all the medicinal plants were retrieved from the ChEBI database, and their targets were predicted using DIGEP-Pred. STRING database and Cytoscape were used to predict the protein-protein interaction and construct the network, respectively. Likewise, MolSoft and admet SAR2.0 were used to predict the druglikeness score and ADMET profile of phytoconstituents. The study identified the modulation of HIF-1, p53, PI3K-Akt, MAPK, cAMP, Ras, Wnt, NF-kappa B, IL-17, TNF, and cGMP-PKG signaling pathways to boost the immune system. Further, multiple pathways were also identified which are involved in the regulation of pathogenesis of the multiple infections and non-infectious diseases due to the lower immune system. Results indicated that the recommended herbal formulation not only modulated the pathways involved in boosting the immunity but also modulated the multiple pathways that are contributing to the progression of multiple disease pathogenesis which would add the beneficial effect in the co-morbid patients of hypertension and diabetes. The study provides the scientific documentation of the role of the Ayurvedic formulation to combat COVID-19.

Oral toxicity evaluation of gokshuradi guggulu, an ayurvedic formulation.

Gokshuradi guggulu is an important classical polyherbal formulation used in Ayurvedic system of medicine for the treatment of various chronic diseases like kidney stones and diabetes. However, no scientific attempts were made to evaluate its oral toxicity. Hence, the present study evaluated the acute and 28 days repeated dose sub-acute oral toxicities of gokshuradi guggulu in rats. Gokshuradi guggulu was tested for its compliance using physicochemical and analytical parameters as per standards prescribed in Ayurvedic Pharmacopeia of India. In acute oral toxicity study, Wistar rats were orally administered a single dose of gokshuradi guggulu (2700 mg/kg) and clinical signs and mortality or moribund stage were observed for 14 days along with weekly body weight. On day 15, the rats were euthanized and the gross morphology was carried out during necropsy. In sub-acute (repeated dose) oral toxicity study, the rats were orally administered gokshuradi guggulu (270, 1350 and 2700 mg/kg) once daily up to 28 days. Clinical signs and mortality or moribund stage, weekly body weight, weekly feed and water consumptions, biochemical and hematological investigations, urine analysis, and major organ weights and histopathology were carried out. In acute and sub-acute toxicity studies, gokshuradi guggulu administration did not show any alteration in parameters or any adverse effect as compared to vehicle treated group. There was no mortality or moribund state observed in any group in both studies. Administration of gokshuradi guggulu in acute and 28 days repeated doses did not exhibit any toxicity or adverse effect at the doses used and NOAEL was found to be 2700 mg/kg.

Anti-mycobacterial Constituents from Medicinal Plants; A Review.

Effective treatment of tuberculosis has been hampered by the emergence of drug-resistant strains of Mycobacterium therapeutic facilities tuberculosis. With the global resurgence of tuberculosis with the development of multidrug-resistant cases, there is a call for the development of new drugs to combat these diseases. Throughout history, natural products have afforded a rich source of compounds that have found many applications in the fields of medicine, pharmacy and biology, and continued to play a significant role in the drug discovery and development process. This review article depicts the various potential plant extracts as well as plant derived phytoconstituents against the H37rv, the most persistent strains of Mycobacterium tuberculosis and its multidrug strains.

Nephroprotective potential of Anogeissus latifolia Roxb. (Dhava) against gentamicin-induced nephrotoxicity in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Stem bark of Anogeissus latifolia Roxb. (Family: Combretaceae) is used traditionally and ethnomedicinally for correction of kidney disorders. AIM OF THE STUDY: The present study demonstrates the nephroprotective potential of stem bark of A. latifolia Roxb. MATERIALS AND METHODS: The HPTLC fingerprint and HPLC analysis were carried out to standardize the ethanolic extract of stem bark of A. latifolia (ALEE) using ellagic acid as a marker. Nephrotoxicity was induced in adult Wistar albino rats by gentamicin (100 mg/kg, intraperitoneally for 8 days) and they were treated with ALEE (100, 200 and 400 mg/kg, orally for 8 days), ellagic acid (10 mg/kg, orally for 8 days) and cystone syrup (5 ml/kg, orally), a standard reference a polyherbal formulation. Urine volume, serum and urine levels of creatinine, urea and uric acid, oxidative stress parameters (lipid peroxidation, catalase, superoxide dismutase and reduced glutathione), inflammatory markers (TNF-α and IL-6) and kidney weight along with its histological changes were studied in experimental animals. RESULTS: HPTLC, HPLC and LC-MS analysis of ALEE revealed the presence of ellagic acid and other various phytoconstituents. Administration of gentamicin caused significant increase in urine output and kidney weight, elevated biochemical, inflammatory and oxidative stress parameters as well as caused histological damage in the kidney tissue. These parameters were attenuated by the concurrent treatment with ALEE and ellagic acid. The effects were comparable to cystone. CONCLUSION: Present investigations concluded that ALEE exhibited nephroprotective potential and validated the traditional use of stem bark of A. latifolia in kidney disorders. The nephroprotective effect may be attributed to the antioxidant and anti-inflammatory phytoconstituents in ALEE.

Computational assessment of saikosaponins as adjuvant treatment for COVID-19: molecular docking, dynamics, and network pharmacology analysis.

Saikosaponins are major biologically active triterpenoids, usually as glucosides, isolated from Traditional Chinese Medicines (TCM) such as Bupleurum spp., Heteromorpha spp., and Scrophularia scorodonia with their antiviral and immunomodulatory potential. This investigation presents molecular docking, molecular dynamics simulation, and free energy calculation studies of saikosaponins as adjuvant therapy in the treatment for COVID19. Molecular docking studies for 23 saikosaponins on the crystal structures of the extracellular domains of human lnterleukin-6 receptor (IL6), human Janus Kinase-3 (JAK3), and dehydrogenase domain of Cylindrospermum stagnale NADPH-oxidase 5 (NOX5) were performed, and selected protein-ligand complexes were subjected to 100 ns molecular dynamics simulations. The molecular dynamics trajectories were subjected to free energy calculation by the MM-GBSA method. Molecular docking and molecular dynamics simulation studies revealed that IL6 in complex with Saikosaponin_U and Saikosaponin_V, JAK3 in complex with Saikosaponin_B4 and Saikosaponin_I, and NOX5 in complex with Saikosaponin_BK1 and Saikosaponin_C have good docking and molecular dynamics profiles. However, the Janus Kinase-3 is the best interacting partner for the saikosaponin compounds. The network pharmacology analysis suggests saikosaponins interact with the proteins CAT Gene CAT (Catalase) and Checkpoint kinase 1 (CHEK1); both of these enzymes play a major role in cell homeostasis and DNA damage during infection, suggesting a possible improvement in immune response toward COVID-19.

Cytotoxic and antiproliferative activity of kanchnar guggulu, an Ayurvedic formulation.

OBJECTIVE: Kanchnar guggulu is a compound Ayurvedic formulation used in clinical practice for the treatment of benign and malignant tumors. The present study investigates its cytotoxic and antiproliferative activities. METHODS: The hydro-alcoholic (50%) extract of kanchnar guggulu was prepared. Its antimitotic activity was assessed in an Allium cepa assay, while its antiproliferative effects were studied in a yeast proliferation model. Methotrexate was used as a standard anticancer agent. RESULTS: In the Allium assay, all concentrations of the extract (1, 2 and 3 mg/mL) and methotrexate (0.02 mg/mL) significantly inhibited the division of A. cepa root cells, decreasing root growth and mitotic index compared to control; this effect was concentration-dependent for kanchnar guggulu extract. In the antiproliferative studies, treatment with the hydro-alcoholic extract of kanchnar guggulu (1, 5 and 10 mg/mL) and methotrexate (0.025, 0.05 and 0.1 mg/mL) resulted in marked reduction of dividing Saccharomyces cerevisiae cells and inhibition of cell viability compared to control. The cytotoxicity of the hydro-alcoholic extract of kanchnar guggulu, shown by its antimitotic and antiproliferative effects, may be due to the presence of flavonoids and phenolics. CONCLUSION: Kanchnar guggulu exhibited a cytotoxic effect by inhibiting cell division (antimitotic) and reducing cell proliferation. These results substantiate its potential for the treatment of cancer and support its traditional use in the treatment of cancer.

Antioxidant and anti-inflammatory activities of Aerva pseudotomentosa leaves.

CONTEXT: Aerva pseudotomentosa Blatt. & Hallb. (Amaranthaceae), commonly called "Bui";, is a medicinal plant of the arid region. It is used for the treatment of inflammatory disorders, such as rheumatic pain, and healing of wounds, which are associated with oxidative stress. OBJECTIVE: The present study evaluated the antioxidant potential of Aerva pseudotomentosa leaves by in vitro models and its anti-inflammatory effect in rats. MATERIAL AND METHODS: The aqueous extract (APAE) was analyzed by HPTLC and HPLC. The antioxidant effect of APAE was evaluated by various in vitro methods [DPPH (1, 1-diphenyl-2-picryl-hydrazil) and hydrogen peroxide free radical scavenging, reducing power, and anti-lipid peroxidation assays]. Anti-inflammatory effect was studied in carrageenan and formalin-induced paw oedema models in rats. APAE (200 and 400 mg/kg) and standard drug, indomethacin (10 mg/kg), were administered orally 1 h before carrageenan/formalin administration and inflammation was noted up to 5 h. RESULTS: HPLC analysis of APAE revealed the presence of rutin. APAE showed significant scavenging effect on DPPH (IC50 49.37 µ g/mL) and peroxide (IC50 288.2 µ g/mL) radicals. The extract exhibited reducing potential and inhibition of lipid peroxidation. APAE treatment significantly attenuated mean increase in paw volume and exhibited inhibition of paw oedema in both in vivo models with inhibition of 45.11% and 49.42%, respectively at 5 h. DISCUSSION AND CONCLUSION: APAE exhibited in vitro antioxidant and anti-inflammatory activities. Anti-inflammatory effect of APAE may be attributed to its antioxidant potential, due to the presence of rutin and other phenolics. This study substantiates folk use of leaves in inflammatory disorders.

Beneficial effect of Amorphophallus paeoniifolius tuber on experimental ulcerative colitis in rats.

CONTEXT: The tuber of Amorphophallus paeoniifolius (Dennst.) Nicolson (Araceae), commonly called Suran or Jimmikand, has high medicinal value and is used ethnomedicinally for the treatment of different gastrointestinal and inflammatory disorders. OBJECTIVE: The present study evaluated the effects of extracts of Amorphophallus paeoniifolius tubers on acetic acid-induced ulcerative colitis (UC) in rats. MATERIALS AND METHODS: Wistar rats were orally administered methanol extract (APME) or aqueous extract (APAE) (250 and 500 mg/kg) or standard drug, prednisolone (PRDS) (4 mg/kg) for 7 days. On 6th day of treatment, UC was induced by transrectal instillation of 4% acetic acid (AA) and after 48 h colitis was assessed by measuring colitis parameters, biochemical estimations and histology of colon. RESULTS: APME or APAE pretreatment significantly (p < .05-.001) prevented AA-induced reduction in body weight and increase in colitis parameters viz. stool consistency, colon weight/length ratio and ulcer score, area and index. Extracts treatment attenuated (p < .001) increase in alkaline phosphatase and lactate dehydrogenase in serum and myeloperoxidase activity and cytokines in colon tissue due to AA administration. Extracts treatment prevented AA-induced elevation in lipid peroxidation and decline in activities of superoxide dismutase and catalase and reduced-glutathione content (p < .05-.001) along with histopathological alterations. PRDS also showed similar ameliorative effect on colitis. DISCUSSION AND CONCLUSION: APME and APAE showed a preventive effect on UC, and ameliorated inflammation and oxidative damage in colon. The effects may be attributed to presence of phytochemicals, betulinic acid, ß-sitosterol, and glucomannan. In conclusion, the tuber of Amorphophallus paeoniifolius exhibited an anticolitic effect through anti-inflammatory and antioxidant action.

Chenopodium album Linn. leaves prevent ethylene glycol-induced urolithiasis in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: The leaves of Chenopodium album Linn. are traditionally used for correction of kidney diseases and urinary stones. The present work investigated the effect of methanolic and aqueous extracts of leaves of Chenopodium album on experimentally-induced urolithiasis in rats to substantiate its traditional use as antilithiatic agent. MATERIALS AND METHODS: The leaf extract was standardized by HPLC. Urolithiasis was induced in rats by administration of 0.75% v/v of ethylene glycol (EG) in distilled water and in addition, vehicle or methanol (CAME) or aqueous (CAAE) extract of the leaves of Chenopodium album each in the dose 100, 200 and 400mg/kg or Cystone (750mg/kg) were administered daily orally for 28 days. Urolithiasis was assessed by estimating the calcium, phosphorus, urea, uric acid, and creatinine in both urine and plasma. The volume, pH and oxalate levels were also estimated in urine. The renal oxalate content was estimated in kidney while calcium oxalate deposits were observed histologically. RESULTS: The treatment with CAME or CAAE for 28 days significantly attenuated the EG-induced elevations in the urine and plasma levels of calcium, phosphorus, urea, uric acid and creatinine along with decrease in urine volume, pH and oxalates. The treatments also decreased renal tissue oxalate and deposition of oxalate crystals in kidney due to EG treatment. The effects of CAME and CAAE were comparable to standard antilithiatic agent, cystone. The findings indicate the preventive effect of CAME and CAAE which can be due to inhibitory effect on crystallization and stone dissolution. The effect was attributed to the presence of phytochemicals like flavonoids and saponins. CONCLUSION: In conclusion, Chenopodium album leaves exhibited antilithiatic effect and validates its ethnomedicinal use in urinary disorders and kidney stones.

Antidiabetic activity of Chandraprabha vati - A classical Ayurvedic formulation.

BACKGROUND: Chandraprabha vati is a classical Ayurvedic formulation, markedly used for mitigation of Prameha, which correlates in many ways with obesity, metabolic syndrome and diabetes mellitus. OBJECTIVE: The present study was aimed to investigate effect of Chandraprabha vati in experimentally-induced hyperglycemia and lipid profile alterations. MATERIALS AND METHODS: Antidiabetic effect of Chandraprabha vati was studied in fifty five Wistar rats. Graded doses of Chandraprabha vati (50, 100 and 200 mg/kg) were administered orally for 7 days to normal and alloxan-hyperglycemic rats (65 mg/kg, intravenously), and to glucose loaded normal rats for oral glucose tolerance test (OGTT). Fasting plasma glucose levels were assessed on different time intervals along with plasma cholesterol and triglycerides. Metformin (500 mg/kg, orally) was used as standard drug. RESULTS: Chandraprabha vati did not cause any significant reduction in plasma glucose levels of normal rats (p > 0.05) but normalized the impaired glucose tolerance at 60 and 120 min (p < 0.05-p < 0.001) in OGTT when compared to vehicle control. In alloxan-hyperglycemic rats, administration of Chandraprabha vati (200 mg/kg) significantly reduced plasma glucose at 3 h, 12 h, 3rd day and 7th day (p < 0.01-p < 0.001) along with reduction in cholesterol and triglycerides levels (p < 0.01-p < 0.001) when compared to diabetic control group. The effects were comparable with metformin. CONCLUSIONS: Chandraprabha vati exhibited anti-hyperglycemic effect and attenuated alterations in lipid profile. The results support the use of Chandraprabha vati for correction of Prameha in clinical practice.

Curative effect of Amorphophallus paeoniifolius tuber on experimental hemorrhoids in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Amorphophallus paeoniifolius (Dennst.) Nicolson (Family- Araceae) is a crop of south East Asian origin. In India, its tuber is widely used in ethnomedicinal practices by different tribes for the treatment of piles (hemorrhoids). AIM: The present study evaluated the effect of methanolic and aqueous extract of Amorphophallus paeoniifolius tuber on croton oil induced hemorrhoids in rats. MATERIALS AND METHODS: The methanolic extract was standardized with the major phenolic compound, betulinic acid, by HPLC. The hemorrhoids were induced by applying 6% croton oil preparation in the ano-rectal region. Rats were orally administered methanolic and aqueous extract at doses of 250 and 500mg/kg, each for 7 days. Pilex (200mg/kg) was used as reference anti-hemorrhoidal drug. Hemorrhoids were assessed on eighth day by measuring hemorrhoidal and biochemical parameters along with histology of ano-rectal tissue. RESULTS: Croton oil application caused induction of hemorrhoids as indicated by significant (p<0.001) increase in plasma exudation of Evans blue in ano-rectal tissue, macroscopic severity score and ano-rectal coefficient as compared to normal rats. It significantly (p<0.001) elevated lactate dehydrogenase and cytokines (TNF-α and IL-6) levels in serum and increased myeloperoxidase activity and lipid peroxidation in ano-rectal tissue along with marked histological damage as compared to normal rats. Treatment with tuber extracts and pilex significantly (p<0.05-p<0.001) ameliorated Evans blue exudation, hemorrhoidal parameters and other biochemical parameters with attenuation of tissue damage compared to hemorrhoid control rats. The results indicate that tuber extracts exhibited curative action on hemorrhoids. The aqueous extract showed more pronounced effect than methanolic extract. The effects may be attributed to anti-inflammatory and antioxidant properties. CONCLUSION: Results indicate that tuber of Amorphophallus paeoniifolius exhibited curative action on hemorrhoids through anti-inflammatory and antioxidant properties. The study validates the ethnomedicinal use of tuber in hemorrhoids and implicates its therapeutic potential as an anti-hemorrhoidal agent.

A phytopharmacological review on an important medicinal plant - Amorphophallus paeoniifolius.

Amorphophallus paeoniifolius is used for long period in various chronic diseases therapeutically. Aim of the current review is to search literature for the pharmacological properties, safety/toxicity studies, pharmacognostic studies and phytochemical investigation of Amorphophallus paeoniifolius tuber. The compiled data may be helpful for the researchers to focus on the priority areas of research yet to be discovered. Complete information about the plant has been collected from various books, journals and Ayurvedic classical texts like Samhitas, Nighantus etc. Journals of the last 20 years were searched. Particulars of pharmacological activities, phytochemical isolation, toxicity studies etc. were extracted from the published reports focussing on the safety profile of the plant. Safety of the whole plant was concluded in the review.