Effect of new polyherbal formulations DF1911, DF2112 and DF2813 on CFA induced inflammation in rat model.

BACKGROUND: Aim of the present study was to evaluate anti-inflammatory activity of newly developed polyherbal formulations DF1911, DF2112 and DF2813. These newly developed formulations are modifications of Dashamoola, a well known Ayurvedic formulation, along with addition of new plants. METHODS: Complete Freund's adjuvant (CFA) induced inflammation in rat was used as an experimental model. Effects of the treatment in rats were monitored by physiological and biochemical parameters, histopathology and through gene expression studies. RESULTS: Diclofenac sodium showed maximum percentage inhibition (56.8 ± 3.5%) of paw edema followed by Dashamoola Kwatha (19.9 ± 1.8%). Among test formulations treated groups, DF1911 at 250 mg/kg bw (48.2 ± 5.4%, p < 0.001) and DF2112 at 250 mg/kg bw (49.9 ± 3.5%, p < 0.001) showed significant and maximum increase in percentage inhibition of paw edema as compared to Dashamoola Kwatha. Hematological alterations in CFA rats were normalized after treatment with test formulations. Results of serum markers and histopathological observations also supported the activity of formulations. Increased MDA levels in liver tissue of CFA injected animals significantly (p < 0.05) decreased by Diclofenac sodium and test formulation treated groups. DF1911, DF2112 and DF2813 showed down-regulation of IL1-ß (~6.4-fold, ~5.2-fold and ~7.6-fold), IL-6 (~1.1-fold, ~1.6-fold and ~1.9-fold), TNF-α (~2.0-fold, ~4.6-fold and ~3.5-fold), and iNOS (~1.2-fold, ~1.8-fold and ~1.1-fold) in inflamed paw tissue compared to negative control group, respectively. CONCLUSIONS: The anti-inflammatory effects of DF1911 and DF2112 in rats were significantly higher than the Dashamoola Kwatha and are comparable to Diclofenac sodium.

New herbal composition (OA-F2) protects cartilage degeneration in a rat model of collagenase induced osteoarthritis.

BACKGROUND: Prevalence of osteoarthritis (OA) is on rise on the global scale. At present there are no satisfactory pharmacological agents for treating OA. Our previous study showed that Sida cordifolia L. and Zingiber officinale Rosc. had protective effect on cartilage. Here, we describe the effect of OA-F2, a herbal formulation prepared using combination of these two plants in alleviating OA associated symptoms in a rat model of collagenase-induced OA. METHODS: OA was induced by intra-articular injection of collagenase type II in wistar rats. Diclofenac (10 mg/kg) was used as a reference control. Rats (n = 6) were divided into 6 groups: Healthy control (HC), osteoarthritic control (OAC), diclofenac (DICLO), OA-F2L (135 mg/kg), OA-F2M (270 mg/kg) and OA-F2H (540 mg/kg). The effects of the 20 days treatment were monitored by parameters like knee diameter, paw volume, paw retraction; serum C-reactive protein (CRP), alkaline phosphatase (ALP) and glycosaminoglycan (GAG). Radiography and histopathology of knee joint were also studied. Additionally, gene expression was studied from isolated synovium tissue proving anti-osteoarthritic potential of OA-F2. RESULTS: Oral administration of OA-F2 has significantly prevented knee swelling compared to OAC; OA-F2 and DICLO, significantly reduced paw volume compared to OAC. Paw latency was remarkably increased by OA-F2 compared to OAC. OA-F2L (-0.670, p < 0.001), M (-0.110, p < 0.05) and H (0.073) has markedly reduced levels of CRP compared to DICLO. OA-F2L (p < 0.05), M (p < 0.001) and H (p < 0.05) significantly reduced ALP levels, compared to DICLO. GAG release in the serum was also significantly lowered in OA-F2 treated group compared to DICLO. Radiological and histopathological observations showed cartilage protection by OA-F2. OA-F2 has upregulated SOD and GPx. Upregulated CAT expression was observed in OA-F2M and H. Considerable down-regulation of expression of MMP-3 and MMP-9 was observed in all the groups. Up-regulation of TIMP-1 was observed in rats treated with OA-F2L, H and DICLO. CONCLUSION: OA-F2 has shown therapeutic effects in rat model of collagenase induced OA by demonstrating cartilage protection through controlling MMPs and improving anti-oxidant levels in arthritic synovium and is a potent candidate for further drug development and treatment for OA.

Anti-fatigue effect of Amarkand on endurance exercise capacity in rats.

BACKGROUND: Amarkand tubers are routinely used by many Indian tribes as a specialized food for health and longevity but so far there is no scientific evidence for their activities. Taxonomically, Amarkand belong to genera Eulophia and Dioscorea. METHODS: In this communication, comparative antifatigue potential of Amarkand was analyzed using forced swimming model in rats and evaluated using biomarkers of physical fatigue. RESULTS: Methanol extracts of tubers of D. bulbifera, E. ochreata, E. leghapanensis and bulbils of D. bulbifera exhibited rich polyphenolic content. D. bulbifera bulbils and E. ochreata significantly prolonged the swimming endurance time. Creatine kinase and urea nitrogen were significantly reduced by treatment of D. bulbifera bulbils and E. ochreata as compared to negative control. D. bulbifera bulbils effectively increased creatine (p < 0.001), lactate dehydrogenase (p < 0.01) and hemoglobin (p < 0.001) compared to negative control. D. bulbifera bulbils and E. ochreata treatments significantly increased glycogen (p < 0.05, p < 0.01) and lowered malondialdehyde levels (p < 0.001) in muscles and in liver tissue compared to negative control. CONCLUSION: These results indicate that a treatment with D. bulbifera bulbils and tubers of E. ochreata facilitates aerobic glucose metabolism and endurance by improving various impairments associated with fatigue.

Hepatoprotective effect of withanolide-rich fraction in acetaminophen-intoxicated rat: decisive role of TNF-α, IL-1ß, COX-II and iNOS.

CONTEXT: Overdose of acetaminophen (APAP) is common in humans and is often associated with hepatic damage. Withania somnifera (L.) Dunal (Solanaceae) shows multiple pharmacological activities including antioxidant and anti-inflammatory potential. OBJECTIVE: To evaluate the possible mechanism of hepatoprotective activity of withanolide-rich fraction (WRF) isolated from a methanolic extract of Withania somnifera roots. MATERIALS AND METHODS: Hepatotoxicity was induced by oral administration of APAP (750 mg/kg, p.o.) for 14 d. The control group received the vehicle. APAP-treated animals were given either silymarin (25 mg/kg) or graded doses of WRF (50, 100 and 200mg/kg) 2 h prior to APAP administration. Animals were killed on 15th day and blood and liver tissue samples were collected for the further analysis. RESULTS: In WRF-treated group, there was significant and dose-dependent (p < 0.01 and p < 0.001) decrease in serum bilirubin, ALP, AST and ALT levels with significant and dose-dependent (p < 0.01 and p < 0.001) increase in hepatic SOD, GSH and total antioxidant capacity. The level of MDA and NO decreased significantly (p < 0.01) by WRF treatment. Up-regulated mRNA expression of TNF-α, IL-1ß, COX-II and iNOS was significantly down-regulated (p < 0.001) by WRF. Histological alternations induced by APAP in liver were restored to near normality by WRF pretreatment. CONCLUSION: WRF may exert its hepatoprotective action by alleviating inflammatory and oxido-nitrosative stress via inhibition of TNF-α, IL-1ß, COX-II and iNOS.

Effect of macronutrient deficiency on withanolides content in the roots of Withania somnifera and its correlationship with molybdenum content.

CONTEXT: The content of withanolides in the roots of Withania somnifera (L.) Dunal (Solanaceae) is important for therapeutic application. Earlier studies have shown that the deficiency of macro- and micronutrients affects the growth of W. somnifera. Therefore, we examined the effect of these deficiencies on the withanolides content of the roots. OBJECTIVE: To examine the effect of molybdenum accretion in nitrogen-, phosphorus-, calcium- and potassium-deficient soils on the accumulation of withanolides in the roots of W. somnifera. Different withanolides have different therapeutic applications hence major bioactive withanolides assume importance. MATERIALS AND METHODS: Methanol extracts of the roots were subjected to HPTLC and individual withanolides were identified by comparing their Rf values with those of the authentic samples. Molybdenum was quantified by atomic absorption spectroscopy. Free radical scavenging activity was monitored by the 1,1-diphenyl-2-picryl-hydrazyl (DPPH) assay. RESULTS: Molybdenum content in roots of nitrogen-, phosphorus-, calcium-, potassium-deficient, and control plants were 7.02 ± 2.1, 13.1 ± 1.6, 17.1 ± 0.9, 33.5 ± 3.3, and 33.9 ± 1.6 ppm, respectively. Levels of withaferine A increased with the increase in the Mo content in roots from 7.79 ± 2.2 mg/g to 12.57 ± 3.4 mg/g. Antioxidant activity of nitrogen-deficient plants was the lowest (24.7 ± 2.2%) compared to other groups. DISCUSSION AND CONCLUSION: It was observed that nitrogen metabolism-dependent molybdenum uptake influences the withanolides accumulation in the roots.

Reviewing the potential of probiotics, prebiotics and synbiotics: advancements in treatment of ulcerative colitis.

Inflammatory bowel diseases (IBD) like Crohn's and ulcerative colitis (UC) are multifactorial pathologies caused by environmental factors and genetic background. UC is a chronic inflammatory disorder that specifically targets the colon, resulting in inflammation. Various chemical interventions, including aminosalicylates, corticosteroids, immunomodulators, and biological therapies, have been extensively employed for the purpose of managing symptoms associated with UC. Nevertheless, it is important to note that these therapeutic interventions may give rise to undesirable consequences, including, but not limited to, the potential for weight gain, fluid retention, and heightened vulnerability to infections. Emerging therapeutic approaches for UC are costly due to their chronic nature. Alternatives like synbiotic therapy, combining prebiotics and probiotics, have gained attention for mitigating dysbiosis in UC patients. Prebiotics promote beneficial bacteria proliferation, while probiotics establish a balanced gut microbiota and regulate immune system functionality. The utilisation of synbiotics has been shown to improve the inflammatory response and promote the resolution of symptoms in individuals with UC through the stimulation of beneficial bacteria growth and the enhancement of intestinal barrier integrity. Hence, this review article aims to explore the potential benefits and underlying reasons for incorporating alternative approaches in the management of UC with studies performed using prebiotics, probiotics, and synbiotics to treat ulcerative colitis and to highlight safety and considerations in UC and future perspectives. This will facilitate the utilisation of novel treatment strategies for the safer and more efficacious management of patients with UC.

Phytochemicals in the treatment of inflammation-associated diseases: the journey from preclinical trials to clinical practice.

Advances in biomedical research have demonstrated that inflammation and its related diseases are the greatest threat to public health. Inflammatory action is the pathological response of the body towards the external stimuli such as infections, environmental factors, and autoimmune conditions to reduce tissue damage and improve patient comfort. However, when detrimental signal-transduction pathways are activated and inflammatory mediators are released over an extended period of time, the inflammatory process continues and a mild but persistent pro-inflammatory state may develop. Numerous degenerative disorders and chronic health issues including arthritis, diabetes, obesity, cancer, and cardiovascular diseases, among others, are associated with the emergence of a low-grade inflammatory state. Though, anti-inflammatory steroidal, as well as non-steroidal drugs, are extensively used against different inflammatory conditions, they show undesirable side effects upon long-term exposure, at times, leading to life-threatening consequences. Thus, drugs targeting chronic inflammation need to be developed to achieve better therapeutic management without or with a fewer side effects. Plants have been well known for their medicinal use for thousands of years due to their pharmacologically active phytochemicals belonging to diverse chemical classes with a number of these demonstrating potent anti-inflammatory activity. Some typical examples include colchicine (alkaloid), escin (triterpenoid saponin), capsaicin (methoxy phenol), bicyclol (lignan), borneol (monoterpene), and quercetin (flavonoid). These phytochemicals often act via regulating molecular mechanisms that synergize the anti-inflammatory pathways such as increased production of anti-inflammatory cytokines or interfere with the inflammatory pathways such as to reduce the production of pro-inflammatory cytokines and other modulators to improve the underlying pathological condition. This review describes the anti-inflammatory properties of a number of biologically active compounds derived from medicinal plants, and their mechanisms of pharmacological intervention to alleviate inflammation-associated diseases. The emphasis is given to information on anti-inflammatory phytochemicals that have been evaluated at the preclinical and clinical levels. Recent trends and gaps in the development of phytochemical-based anti-inflammatory drugs have also been included.

Rectal gel application of Withania somnifera root extract expounds anti-inflammatory and muco-restorative activity in TNBS-induced inflammatory bowel disease.

BACKGROUND: Inflammatory Bowel Disease (IBD) is marked with chronic inflammation of intestinal epithelium driven by oxidative stress. Traditional treatments with plant extracts gained renewed interest due to their ability to ameliorate the multi factorial conditions like inflammation. We investigated the beneficial effects of Withania somnifera in Trinitro Benzyl Sulfonic Acid (TNBS) induced experimental IBD through a rectally applicable formulation. METHODS: The study included (i) preparation of gel formulation from aqueous Withania somnifera root extract (WSRE), (ii) biochemical assays to determine its performance potential, (iii) testing of formulation efficacy in TNBS-induced IBD rat model, and (iv) histo-patholgical studies to assess its healing and muco-regenerative effect in IBD-induced rats. For this purpose, concentration dependant antioxidant activity of the extracts were evaluated using biochemical assays like (a) inhibition of lipid peroxidation, (b) NO scavenging, (c) H2O2 scavenging, and (d) ferric reducing power assay. RESULTS: The extract, at 500 µg/ml, the highest concentration tested, showed 95.6% inhibition of lipid peroxidation, 14.8% NO scavenging, 81.79% H2O2 scavenging and a reducing capacity of 0.80. The results were comparable with standard antioxidants, ascorbic acid and curcumin. WSRE treatment positively scored on histopathological parameters like necrosis, edema, neutrophil infiltration. The post treatment intestinal features showed restoration at par with the healthy intestine. In view of these results, gel formulation containing an aqueous extract of W. somnifera, prepared for rectal application was tested for its anti-inflammatory activity in TNBS-induced rat models for IBD. Commercially available anti-inflammatory drug Mesalamine was used as the standard in this assay. CONCLUSIONS: Dose of the rectal gel applied at 1000 mg of WSRE per kg rat weight showed significant muco-restorative efficacy in the IBD-induced rats, validated by histo-pathological studies.

Computational assessment of select antiviral phytochemicals as potential SARS-Cov-2 main protease inhibitors: molecular dynamics guided ensemble docking and extended molecular dynamics.

Covid-19 caused by novel coronavirus, 2019-nCoV or SARS-CoV-2 has become most severe pandemic of this century. No specific therapies are available to treat Covid-19 so far. Recently, main protease (Mpro), a potential drug target from SARS-CoV-2 has been successfully crystallised. The present study is aimed at assessment of bioactive antiviral phytochemicals as potential SARS-COV-2 Mpro inhibitors, using ensemble docking, molecular dynamics and MM-PBSA calculations. Ensemble docking studies were performed with Autodock vina program. The top 5 compounds having highest binding free energy were subjected to 100 ns molecular dynamics simulations with Gromacs. The resulting trajectories of converged period of MD were further exploited in MM-PBSA calculations to derive accurate estimates of binding free energies. The MD results were analysed with respect to RMSD, RMSF and hydrogen bond formation and occupancy parameters. The drugs remdesivir and nelfinavir were used as standard drugs for comparative studies. In the docking studies five phytochemicals, dalpanitin, amentoflavone, naringin, hinokiflavone, and rutin were found having lowest binding free energies (< - 10 kcal mol-1) which is lower than standard drugs. MD studies suggested that the complexes of these five phytochemicals with Mpro stabilize with well accepted RMSD. Amongst these phytochemicals, hinokiflavove, amentoflavone and naringin were found having better binding affinity with ΔGbinging than the standard drug remdesivir. Investigations and validation of these inhibitors against SARS-CoV-2 would be helpful in bring these molecules at the clinical settings. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40203-021-00107-9.

Synovium-Synovial Fluid Axis in Osteoarthritis Pathology: A Key Regulator of the Cartilage Degradation Process.

Failure of conventional anti-inflammatory therapies in osteoarthritis (OA) underlines the insufficient knowledge about inflammatory mechanisms, patterns and their relationship with cartilage degradation. Considering non-linear nature of cartilage loss in OA, a better understanding of inflammatory milieu and MMP status at different stages of OA is required to design early-stage therapies or personalized disease management. For this, an investigation based on a synovium-synovial fluid (SF) axis was planned to study OA associated changes in synovium and SF along the progressive grades of OA. Gene expressions in synovial-biopsies from different grades OA patients (N = 26) revealed a peak of IL-1ß, IL-15, PGE2 and NGF in early OA (Kellgren-Lawrence (KL) grade-I and II); the highest MMP levels were found in advanced stages (KL grade-III and IV). MMPs (MMP-1, 13, 2 and 9) abundance and FALGPA activity estimated in forty SFs of progressive grades showed the maximum protein levels and activity in KL grade-II and III. In an SF challenge test, SW982 and THP1 cells were treated with progressive grade SFs to study the dynamics of MMPs modulation in inflammatory microenvironment; the test yielded a result pattern, which matched with FALGPA and the protein-levels estimation. Inflammatory mediators in SFs served as steering factor for MMP up-regulation. A correlation-matrix of IL-1ß and MMPs revealed expressional negative correlation.

Reduced synovial inflammation and inhibition of matrix metalloproteinases explicates anti-osteoarthritis activity of polyherbal formulations.

OBJECTIVES: Current osteoarthritis (OA) research experiences an incline toward Ayurveda to attain a complete cure without notable adverse effects. Ayurveda uses natural products, which are known to perform the multi-faceted role, a much demanding approach for OA management. However, lack of scientific evidence is a major drawback hindering their wider use. The present work investigated the anti-arthritic potential of Ashwagandharishta, Balarishta, Dashmoolarishta, and Triphala-extract to establish molecular-evidence for their clinical use. MATERIALS AND METHODS: Rabbit synoviocytes were induced using interleukin-1 beta (IL-1 ß) and lipopolysaccharide (LPS) separately and were further treated with study formulations to test anti-inflammatory and anti-oxidant potential, using nitric oxide (NO) and malondialdehyde (MDA) assays. Collagenase inhibition activity was estimated with N-(3-[2-Furyl] acryloyl)-Leu-Gly-Pro-Ala (FALGPA)-substrate and gelatinase spot assays. Data were analyzed with GraphPad Prism using one-way ANOVA followed by Bonferroni's multiple comparison. RESULTS: The study formulations were effective against synovitis, oxidative-stress, and inhibiting collagenase. They caused NO reduction in selected concentrations. DA showed the maximum NO decline of 0.02 ± 0 and 0.97 ± 0.62 µM/ml with IL-1 ß and LPS induction at 5 and 20 µg/ml concentrations, respectively. Estimated by FALGPA assay, increasing collagenase inhibition was observed as the function of concentration. All formulations showed a significant MDA decline, in dose-dependent manner. CONCLUSION: We assessed the anti-OA efficacy of conventionally prescribed Ayurvedic drugs using relevant biochemical assays. The studied formulations revealed potential to restrain synovitis, cartilage degeneration and to reduce oxidative stress, and the signature OA features. With established molecular authenticity, Ayurvedic drugs can offer a safer and affordable therapeutic option for OA.

Herbal remedies for urinary stones used in India and China: A review.

ETHANOPHARMACOLOGICAL RELEVANCE: The process of formation or appearance of a urinary stone anywhere in the renal tract is known as urolithiasis. It is a longstanding health problem, known to exist since early age of civilization. Records about symptoms, signs and treatment strategies of urinary stones diseases are found in the several ancient texts of traditional medicines such as Ayurveda, Traditional Chinese Medicine (TCM), Siddha and Unani. In Ayurveda, urolithiasis has been considered as one of the eight most troublesome diseases. Ayurvedic management and cure of urinary stone involves herbal formulas, alkaline liquids and surgical procedures. Whereas, TCM recommends polyherbal drugs, acupuncture and mexibustion for treatment of the urinary stones. Among these therapies, herbal remedies are in practice till today for the treatment and cure urinary stone diseases. MATERIALS AND METHODS: A comprehensive review of the scientific literature about pathophysiology of urinary stones and antiurolithiatic plants was undertaken using the following bibliographic databases: MEDLINE/PubMed, Scopus, Web of Knowledge and Google Scholar. The search was conducted from publications from all years until Dec., 2015 by combination of the search terms and Boolean operators; 'urinary stone' OR 'kidney stone' AND 'plant' OR 'medicine' OR 'antiurolithiatic plants'. Outputs were restricted to those completed studies only published in English. In this review, literatures about plants which are used as diuretic and/or in treatment urinary tract infections have not also been considered. The Plant List and Royal Botanical Garden, Kew databases were used to authenticate botanical names of plants. Books and monographs published in English were used to collect information about historical records of antiurolithiatic plants. RESULTS: Recent pharmacological interventions accredited ancient antiurolithiatic claims to several plants and their formulations. The majority of antiurolithiatic plants were found to either dissolve the stones or inhibit the process of urinary stone formation. Plants such as Phyllanthus niruri L. and Elymus repens (L.) Gould, as well as herbal products including 'Wu-Ling-San' formula, 'Cystone' and 'Herbmed' have been proved their utility as promising antiurolithiatic medicines in the different phases of clinical trials. In addition, some of the isolated phytochemicals such as berberine, lupeol, khelin, visnagin, 7-hydroxy-2',4',5'-trimethoxyisoflavone and 7-hydroxy-4'-methoxyisoflavone were reported to have potent antiurolithiatic activity. CONCLUSION: In ancient medicinal texts, antiurolithiatic potential has been ascribed to several plants and their formulations. Present scientific studies provide scientific evidences for few of these claims however, they are insufficient to establish many of these plants and herbal formulations as therapeutic remedies for the treatment and management of urinary stones. Conversely, findings of pre-clinical and clinical studies about some plants and herbal formulations are promising, which underlines the utility of herbal remedies as alternative medicines for the treatment and management of urinary stones in the future.

HPLC, NMR based chemical profiling and biological characterisation of Indian propolis.

The present study aimed to investigate chemical profile, antioxidant and antimicrobial activities of Indian Melifera propolis (IMP) samples collected from 13 different states. Chemical characterisation of ethanolic extracts of IMP (EEMP) samples was carried out by using HPLC and 1HNMR spectroscopy. The antioxidant activity of EEMP samples was measured by DPPH, ABTS, and FRAP assay. Moreover, the antimicrobial activity of each EEMP sample tested against bacteria and yeast using a 96 well plate microdilution method. All EEMP samples had remarkable antioxidant and antimicrobial activities. The antioxidant potential of EEMP samples found to have a moderate positive correlation with their total phenolics and flavonoids content. Majority of EEMP samples had a minimum inhibitory concentration (MIC) ≤1mg/mL against Staphylococcus aureus. Chemometric analysis of 1HNMR data indicated that brown, green, green-brown, red and red-brown coloured IMP samples were chemically distinct from each other, and showed two separate clusters for northern and southern states propolis samples. HPLC analysis confirmed phenethyl caffeate was most common and abundant compound in IMP samples among studied compounds. In conclusion, this study may be helpful for defining the quality of IMP as a raw material, and also in finished food and health care products.

Amarkand: A comprehensive review on its ethnopharmacology, nutritional aspects, and taxonomy.

In India, the term "Amarkand" is commonly used for around 30 different plant species belonging to genus Eulophia (Orchidaceae). This single local name Amarkand to different taxonomical species creates uncertainty about its ethnomedical and nutritional claims. In the present article, we have reviewed available literature regarding ethnopharmacology, phytochemistry, taxonomy, nutritional, and pharmacological studies of different Amarkand species. The literature was searched using Google Scholar, PubMed, Scopus, and Web of Science databases. Some textbooks and reference books were also used to collect information about traditional and ethnopharmacological records. Amarkand species have been used as a remedy for the treatment of various diseases such as diarrhea, stomach pain, rheumatoid arthritis, cancer, asthma, bronchitis, sexual impotency, tuberculosis, and so on. Nutritionally, Amarkand is considered as an excellent food for children and convalescents. Recent studies confirm antioxidant, anti-inflammatory, anti-diarrheal, and so forth activities to Amarkand species. These species are reported to possess various phytoconstituents such as flavonoids, terpenoids, and phenanthrene derivatives. The present review will help to understand overall ethnopharmacology, nutritional aspects, and taxonomy of Amarkand species.

Evaluation of the bioavailability of major withanolides of Withania somnifera using an in vitro absorption model system.

Withania somnifera (L.) Dunal, shows several pharmacological properties which are attributed mainly to the withanolides present in the root. The efficacy of medicinally active withanolides constituents depends on the absorption and transportation through the intestinal epithelium. We examined these characteristics by employing the Sino-Veda Madin-Darby canine kidney cells culture system, which under in vitro condition shows the absorption characteristics similar to the human intestinal epithelium. Thus, the aim of the present investigation was to assess the bioavailability of individual withanolides. Withanolides were diluted in Hank's buffered saline at a concentration of 2 µg/ml were tested for permeability studies carried out for 1 h duration. Permeability was measured in terms of efflux pump (P eff) in cm/s. P eff values of withanolide A (WN A), withanone (WNN), 1,2-deoxywithastramonolide (1,2 DWM), withanolide B (WN B), withanoside IV-V (WS IV-V), and withaferin A were 4.05 × 10(-5), 2.06 × 10(-5), 1.97 × 10(-5), 1.80 × 10(-5), 3.19 × 10(-6), 3.03 × 10(-6) and 3.30 × 10(-7) respectively. In conclusion, the nonpolar and low molecular weight compounds (WN A, WNN, 1,2 DWM, and WN B) were highly permeable. As against this, the glycosylated and polar WS IV and WS V showed low permeability. Surprisingly and paradoxically, the highly biologically active withaferin A was completely impermeable, suggesting that further studies possibly using human epithelial colorectal adenocarcinoma (Caco-2) cells may be needed to delineate the absorption characteristics of withanolides, especially withaferin A.

Influence of six medicinal herbs on collagenase-induced osteoarthritis in rats.

Medicinal herbs have been effectively used for their anti-inflammatory activity, but their exact role has not yet been documented in scientific literature for the management of Osteoarthritis (OA). Since Sida cordifolia L., Piper longum L., Zingiber officinale Rosc., Ricinus communis L., Vitex negundo L. and Tribulus terrestris L. have been widely used in traditional medicine for their anti-inflammatory activity, to evaluate anti-osteoarthritic activity of these herbs, we used a collagenase type II-induced osteoarthritis (CIOA) rat model. Arthritis was induced in wistar rats by intra-articular injection of collagenase type II. Powders of herbs were given orally for 20 days as a suspension in water (270 mg/kg b. wt.). The effects of the treatment in the rats were monitored by physiological parameters like body weight, knee diameter, paw retraction, paw volume, glycosaminoglycan (GAG) release, radiography and histopathology of knee joint. Selected herbs have significantly prevented body weight loss and knee swelling compared to arthritic control (CIOA). All test groups, including indomethacin (standard drug, 3 mg/kg), significantly reduced paw volume compared to CIOA. GAG release in the serum was significantly lowered in herb treated groups compared to indomethacin. The anterior posterior radiographs of S. cordifolia and P. longum treated groups showed a protective effect against OA. Histopathology revealed protection in the structure of the articular cartilage and in chondrocyte pathology as well as reduced clefting. Treatment with herbs has shown chondroid matrix within normal limits. From the results, we observed that S. cordifolia and P. longum possess potent anti-osteoarthritic activity.

Evaluation of comparative free-radical quenching potential of Brahmi (Bacopa monnieri) and Mandookparni (Centella asiatica).

Ayurvedic texts describe rejuvenate measures called Rasayana to impart biological sustenance to bodily tissues. Rasayana acting specifically on brain are called Medhya Rasayana. Brahmi is one of the most commonly practiced herbs for the same. Yet there exist a controversy regarding the exact plant species among Bacopa monnieri L. Penn (BM) and Centella asiatica (L.) Urban (CA) to be used as Brahmi in the formulations. Though the current literature available has suggested a very good nootropic potential of both the drugs, none of the studies have been carried out on comparative potential of these herbs to resolve the controversy. Free-radical scavenging potential for these plants is studied to find out their comparative efficacy. The study revealed a very good in vitro free-radical scavenging properties of aqueous and ethanolic extracts of both the plants as evidenced by FRAP, DPPH, reducing power, and antilipid peroxidation assays. It can be concluded from the studies that both the plants, although taxonomically totally different at family level, showed similar type of in vitro activities. The total phenolic and flavonoid contents also revealed a significant similarity in the two plants. The in vitro study supports the Ayurvedic concept of BM and CA having a similar potential.