Modulation of psoriatic-like skin inflammation by traditional Indian medicine Divya-Kayakalp-Vati and Oil through attenuation of pro-inflammatory cytokines.

Background and aim: Psoriasis (Ps) is a chronic skin inflammatory disorder, that progresses to scaly-red dermal plaque formations associated with inflammation. Divya-Kayakalp-Vati (DKV) and Divya-Kayakalp-Oil (DKO) are traditional Ayurveda herbo-mineral formulations, that are prescribed for the treatment of inflammatory dermal ailments. In the present study, we evaluated the efficacy of Divya-Kayakalp-Vati and Divya-Kayakalp-Oil (DKV-O) combined treatment in ameliorating Ps-like skin inflammation under in-vitro and in-vivo conditions. Experimental procedure: Efficacy of DKV-O was analyzed in λ-carrageenan-treated Wistar rats paw edema and 12-O-tetradecanoylphorbol 13-acetate (TPA)-treated CD-1 mouse ear edema models through physiological and histopathological analysis. Mode of action for the DKV-O was studied in LPS-stimulated THP-1 cells through pro-inflammatory cytokine analysis. Observed effects were correlated to the phytochemicals constituents of DKV-O analyzed using the HPLC method. Result and conclusion: DKV and DKO formulations were individually found to contain phytochemicals Gallic acid, Catechin, Berberine, Curcumin, Phenol and Benzoic acid. DKV-O treatment significantly reduced the paw volume and edema in Wistar rats stimulated through λ-carrageenan-treatment. Furthermore, DKV-O treatment significantly reduced the ear edema and enhanced biopsy weight, epidermal thickness, inflammatory lesions and influx of neutrophils stimulated by TPA-treatment in CD-1 mice. DKV alone ameliorated the LPS-stimulated release of Interleukin (IL)-6, IL-17A, IL-23, and Tumor Necrosis Factor-alpha cytokines in the THP-1 cells.Taken together, DKV-O showed good efficacy in ameliorating acute systemic inflammation stimulated by effectors such as, λ-carrageenan and TPA in animal models. Hence, Divya-Kayakalp-Vati and Divya-Kayakalp-Oil co-treatment can be further explored as an anti-inflammatory treatment against dermal diseases like psoriasis and atopic dermatitis.

Herbal Decoction Divya-Peedantak-Kwath Alleviates Allodynia and Hyperalgesia in Mice Model of Chemotherapy-Induced Peripheral Neuropathy via Modulation in Cytokine Response.

The widely used cancer treatment, chemotherapy, causes severe long-term neuropathic pain in 30-40% cases, the condition clinically known as chemotherapy-induced peripheral neuropathy (CIPN). Approved conventional analgesics are sometimes ineffective, while others like opioids have undesirable side effects like addiction, seizures, and respiratory malfunctioning. Tricyclic antidepressants and anticonvulsants, although exhibit anti-allodynic effects in neuropathy, also have unpleasant side effects. Thus, alternative medicines are being explored for CIPN treatment. Despite scattered reports on different extracts from different plants having potential anti-allodynic effects against CIPN, no established medicine or formulation of herbal origin exists. In this study, efficacy of an herbal decoction, formulated based on ancient medicinal principles and protocols for treating neuropathic pain, Divya-Peedantak-Kwath (DPK), has been evaluated in a paclitaxel (PTX)-induced peripheral neuropathic mouse model. We observed that DPK has prominent anti-allodynic and anti-hyperalgesic effects and acts as a nociceptive modulator for CIPN. With exhibited antioxidative effects, DPK restored the redox potential of the sciatic nerves to the normal. On histopathological evaluation, DPK prevented the PTX-induced lesions in the sciatic nerve, in a dose-dependent manner. It also prevented inflammation by modulating the levels of pro-inflammatory cytokines involved in CIPN pathogenesis. Our observations evinced that DPK can alleviate CIPN by attenuating oxidative stress and concomitant neuroinflammation through immune modulation.

Polyherbal Medicine Divya Sarva-Kalp-Kwath Ameliorates Persistent Carbon Tetrachloride Induced Biochemical and Pathological Liver Impairments in Wistar Rats and in HepG2 Cells.

Divya Sarva-Kalp-Kwath (SKK) is a poly-herbal ayurvedic medicine formulated using plant extracts of Boerhavia diffusa L. (Nyctaginaceae), Phyllanthus niruri L. (Euphorbiaceae), and Solanum nigrum L. (Solanaceae), described to improve liver function and general health. In the present study, we have explored the hepatoprotective effects of SKK in ameliorating carbon tetrachloride (CCl4) induced liver toxicity using in-vitro and in-vivo test systems. Chemical analysis of SKK using Liquid Chromatography-Mass Spectroscopy (LC-MS-QToF) and High-Performance Liquid Chromatography (HPLC) revealed the presence of different bioactive plant metabolites, known to impart hepatoprotective effects. In human hepatocarcinoma (HepG2) cells, co-treatment of SKK with CCl4 effectively reduced the hepatotoxicity induced by the latter. These effects were confirmed by studying parameters such as loss of cell viability; release of hepatic injury enzymatic biomarkers- aspartate aminotransferase (AST), and alkaline phosphatase (ALP); and changes in reactive oxygen species and in mitochondrial membrane potentials. In-vivo safety analysis in Wistar rats showed no loss in animal body weight, or change in feeding habits after repeated oral dosing of SKK up to 1,000 mg/kg/day for 28 days. Also, no injury-related histopathological changes were observed in the animal's blood, liver, kidney, heart, brain, and lung. Pharmacologically, SKK played a significant role in modulating CCl4 induced hepatic injuries in the Wistar rats at a higher dose. In the 9 weeks' study, SKK (200 mg/kg) reduced the CCl4 stimulated increase in the release of enzymes (ALT, AST, and ALP), bilirubin, total cholesterol, and uric acid levels in the Wistar rats. It also reduced the CCl4 stimulated inflammatory lesions such as liver fibrosis, lymphocytic infiltration, and hyper-plasticity. In conclusion, SKK showed pharmacological effects in improving the CCl4 stimulated liver injuries in HepG2 cells and in Wistar rats. Furthermore, no adverse effects were observed up to 10× higher human equivalent dose of SKK during 28-days repeated dose exposure in Wistar rats. Based on the literature search on the identified plant metabolites, SKK was found to act in multiple ways to ameliorate CCl4 induced hepatotoxicity. Therefore, polyherbal SKK medicine has shown remarkable potentials as a possible alternative therapeutics for reducing liver toxicity induced by drugs, and other toxins.

Anti-Inflammatory and Anti-Arthritic Efficacies of an Indian Traditional Herbo-Mineral Medicine "Divya Amvatari Ras" in Collagen Antibody-Induced Arthritis (CAIA) Mouse Model Through Modulation of IL-6/IL-1ß/TNF-α/NFκB Signaling.

Rheumatoid arthritis (RA) is defined as a chronic autoimmune inflammatory disorder that causes damage to limb joints and progressive injuries to secondary organs. Medical practitioners prescribe Methotrexate (MTX) as standard care medicine for treating RA. However, the long-term application of MTX has shown to have adverse health-related effects. Divya Amvatari Ras (DAR), an Indian Ayurvedic herbo-mineral formulation, has been described in ancient texts to provide relief from RA inflammation associated distress. Therefore, in the present study, we explored the biocompatibility, anti-inflammatory, and anti-arthritic efficacy of DAR using in vivo and in vitro disease models. Using carrageenan (CA)-stimulated Wistar rat paw edema model, we showed a reduction in inflammation-induced paw edema at human equivalent dose of DAR. Anti-rheumatic efficacy of DAR was studied using collagen-antibody cocktail (C-Ab) Induced Arthritis (CAIA) mouse model. The onset of RA in the CAIA mice was determined using parameters such as the increase in arthritis score, and induction of disease associated lesions in the ankle and knee joints, and increase in mechanical and thermal hyperalgesia. Treatment of CAIA animals with a human equivalent dose of DAR significantly reversed the RA-associated pathogenesis. These effects were comparable with the standard of care RA drug, MTX. DAR acted at multiple levels of inflammation associated with RA to reduce progressive pathogenesis. Animal serum biochemistry showed DAR was capable of ameliorating RA induced increase in liver enzyme Alanine Aminotransferase (ALT) and pro-inflammatory cytokine interleukin 6 (IL-6). In the lipopolysaccharide stimulated THP-1 cells, DAR was found to inhibit the release of IL-6, IL-1ß, TNF-α, and upstream inflammatory gene regulatory protein, NFκB. The study endorsed the anti-arthritic and anti-inflammatory activity of the Indian Traditional herbo-mineral medicine, DAR. These results also confirm that DAR was highly biocompatible and would show minimal health-related side effects than those associated with standard of care MTX. Taken together, we show that the DAR could be utilized as a promising alternative or complementary therapy for treating rheumatoid arthritis.

Herbo-mineral formulation 'Ashwashila' attenuates rheumatoid arthritis symptoms in collagen-antibody-induced arthritis (CAIA) mice model.

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disorder that affects joints of hands and feet and introduces injury in secondary organs such as cardiac tissue. In the present study, we induced RA in male Balb/c mice (CAIA) using collagen-antibody cocktail (C-Ab) and lipopolysaccharide intraperitoneal injections. Induction of RA in the animals was detected through the loss of body weight, food, and water consumption, pedal edema, increased arthritis score of the paw and ankle, increase in radiological and histological lesion score of ankle and knee joints and enhanced pain perception in the C-Ab induced RA animals. Ashwashila is a herbo-mineral medicine from Indian Ayurvedic system. Human equivalent doses of Ashwashila (ASHW) and standard of care, Methotrexate were given to the CAIA animals for two weeks. ASHW treatment significantly reversed the effect of C-Ab with reduced pedal edema, arthritis score, radiological and histological lesion scores in ankle-joint, knee-joint and articular cartilage, reduced pain perception. These effects were comparable with the Methotrexate treatment. In human monocytic (THP-1) cells, ASHW was found to be biocompatible at in-vitro test doses. The anti-arthritis mechanism of action for ASHW was established through the suppression of pro-inflammatory cytokines such as IL-1ß, IL-6, TNF-α; and upstream regulator, NF-κB. Taken together, we show the pre-clinical efficacy of ASHW in reducing RA associated symptoms by controlling inflammation and suggest it as a potential therapeutic candidate for rheumatoid arthritis.

Evaluation of polyherbal ayurvedic formulation 'Peedantak Vati' for anti-inflammatory and analgesic properties.

ETHNOPHARMACOLOGICAL RELEVANCE: Peedantak Vati (PV) is a polyherbal ayurvedic formulation, which is regularly prescribed by the ayurvedic practitioner for the inflammatory disorders and joints pain in India. It is composed of 23 different herbs and minerals, described in ayurvedic text for their anti-inflammatory and analgesic properties. AIM OF THE STUDY: To investigate anti-inflammatory and anti-nociceptive potential of 'Peedantak Vati' using in vitro and in vivo methods. MATERIALS AND METHODS: In-vitro anti-inflammatory activity of PV was studied by estimating nitric oxide (NO) and LPS-induced pro-inflammatory cytokines IL-6 and TNF-α, using murine macrophage RAW264.7 and human monocyte THP-1 cell lines. PV's anti-inflammatory potential was studied in vivo using carrageenan-induced rat paw edema model. Similarly, anti-nociceptive property of PV was evaluated using hot plate, tail flick, formalin and writhing tests on CD-1 mice. Phytochemical profiling of hydro-alcoholic extract of PV was done using HPLC and HPTLC techniques to identify different marker compounds. These identified marker compounds were confirmed using LC-MS/MS analysis. RESULTS: In vitro results strongly suggest that, PV significantly (p < 0.001) inhibited NO release and LPS-stimulated pro-inflammatory cytokines IL-6 and TNF-α, in murine RAW264.7 and human THP-1 cells. Further, PV demonstrated significant (p < 0.05) anti-inflammatory activity at different time points after carrageenan injection with maximum effect at 2 h (40.4 ±â€¯5.2% at 400 mg/kg). Similarly, PV significantly (p < 0.05) decreased nociceptive pain, studied using hot plate, tail flick, formalin and writhing tests. Moreover, HPLC and HPTLC methods were developed for the standardization of PV. Five marker phytocompounds viz. rutin, caffeic acid, colchicine, withaferin A and curcumin were identified and quantified by HPLC and HPTLC methods. The presence of these phytoconstituents was confirmed by LC-MS/MS analysis. CONCLUSION: The findings of the study strongly suggest that, the polyherbal ayurvedic formulation 'Peedantak Vati' possesses remarkable anti-inflammatory and analgesic property, providing potent alternative for currently available allopathic medicines such as non steroidal anti-inflammatory drugs (NSAIDs).