Peedanil Gold, Herbo-Mineral Formulation, Moderates Cytokine Levels and Attenuates Pathophysiology in Monosodium Iodoacetate Induced Osteoarthritis in SD Rat Model.

The inflammatory cartilaginous degeneration of the articular joints, mostly those of knee, hips and hands, is osteoarthritis (OA). The available treatment strategies for osteoarthritis are designed for pain relief, molecular targeting, cartilage regeneration and surgical intervention. However, meta-analysis of clinical trials has shown these strategies to be sub-optimal, thereby, eliciting a need for investigating alternative options. The herbo-mineral formulation, Peedanil Gold (PN-G) has been used against joint pains and inflammation. In the current study, anti-osteoarthritic effects of PN-G were investigated in rat model of OA, induced by intra-articular injection of monosodium-iodoacetate. PN-G treatment improved the clinical and Kellgren & Lawrence scores; and rescued the osteoarthritic rats from hyperalgesia and allodynia. Besides, PN-G treatment ameliorated joint inflammation and abrogated in vivo osteoarthritic pathology through effective cartilage regeneration, measured radiologically and histopathologically. PN-G also reduced the levels of interleukin-6 (IL-6) and interleukin-1 beta (IL-1ß), in a dose dependent manner, in inflamed human macrophagic THP-1 cells, thereby, reaffirming its anti-inflammatory property at cytosafe concentrations. Ultra High performance liquid chromatography (UHPLC) revealed the presence of several analgesic and anti-inflammatory phytocompounds, like ellagic acid, guggulsterone E, guggulsterone Z, 5-(hydroxymethyl) furfural, corilagin, cinnamic acid, ferulic acid, gallic acid and protocatechuic acid in PN-G. In conclusion, this study has succinctly demonstrated that PN-G is capable of relieving the clinical symptoms of osteoarthritis, which is measurable through the established osteoarthritic serum biomarker, Cartilage Oligomeric Matrix Protein (COMP).

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.

Impact of chronic low dose exposure of monocrotophos in rat brain: Oxidative/ nitrosative stress, neuronal changes and cholinesterase activity.

Monocrotophos (MCP) is an organophosphate mainly used as insecticides in agriculture, and veterinary practice to control pests. Exposure to MCP is known to induce significant systemic toxicity in animals and humans. Short term exposure to a high dose of MCP has been reported to cause systemic toxicity, however limited information is available regarding low dose long term exposure in rats. We studied the effects of low dose long term exposure to MCP on oxidative/nitrosative stress, cholinesterase activity and neuronal loss in rat. Male rats were exposed to MCP (0.1 µg or 1 µg/ml) via drinking water for 8 weeks. The pro-oxidant markers such as reactive oxygen species (ROS), lipid peroxidation (MDA), nitrite level and antioxidant markers such as reduced glutathione (GSH), superoxide dismutase (SOD), catalase (CAT) and inhibition of cholinesterase activities were measured to evaluate the effects of MCP on brain along with plasma cholinesterase activity. Neuronal loss was analyzed in cortical region using H&E stained slices. The results suggested that exposure to MC even at the low dose, increased reactive oxygen species, thiobarbituric acid reactive substance levels and decreased glutathione, superoxide dismutase, catalase and cholinesterase activities in brain. No significant effect however, was observed on nitrite levels. Histological analysis revealed that low dose MCP exposure lead to structural changes in the cortical neurons in rats. It can be concluded from the study that low dose long term exposure (lower than No Observed Effect Level) of MCP may lead to the generation of oxidative stress by elevation of pro-oxidants markers and depletion of antioxidant enzymes markers along with inhibition of cholinesterase activity. These changes might thus be considered as the possible mechanism of cortical neuronal loss in these animals.