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      Polyherbal formulation PL02 alleviates pain, inflammation, and subchondral bone deterioration in an osteoarthritis rodent model

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          Abstract

          Introduction

          Osteoarthritis (OA) is a debilitating disease with significant personal and socioeconomic burdens worldwide.

          Methods

          To address this, we developed a multitargeted formulation called PL02, which includes standardized extracts of Rosa canina L, Hippophae rhamnoides, and collagen peptide. We tested the pharmacological efficacy of PL02 in a rodent model of OA induced by Monosodium iodoacetate (MIA).

          Results

          Our results demonstrate that oral administration of PL02 has antioxidant effects by down-regulating NOS, reduces pain-related behavior, and mitigates inflammation by inhibiting IL-1b and TNF-α production, as well as downregulating CGRP1 and COX-II. PL02 also exhibits anti-catabolic and chondroprotective activity by significantly downregulating MMP13 and upregulating BCL2. Additionally, PL02 demonstrates chondrogenic activity by significantly upregulating SOX-9 (a master regulator of chondrogenesis), Coll-I, and aggrecan, which are major components of articular cartilage. Furthermore, PL02 prevents microarchitectural deterioration of subchondral bone.

          Conclusion

          Overall, PL02 is an orally active, multi-targeted therapy that not only alleviates pain and inflammation but also effectively halts cartilage and subchondral bone deterioration. It represents a safe and promising candidate for the treatment and management of OA.

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          Most cited references65

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          Quantitative assessment of tactile allodynia in the rat paw

          We applied and validated a quantitative allodynia assessment technique, using a recently developed rat surgical neuropathy model wherein nocifensive behaviors are evoked by light touch to the paw. Employing von Frey hairs from 0.41 to 15.1 g, we first characterized the percent response at each stimulus intensity. A smooth log-linear relationship was observed, with a median 50% threshold at 1.97 g (95% confidence limits, 1.12-3.57 g). Subsequently, we applied a paradigm using stimulus oscillation around the response threshold, which allowed more rapid, efficient measurements. Median 50% threshold by this up-down method was 2.4 g (1.81-2.76). Correlation coefficient between the two methods was 0.91. In neuropathic rats, good intra- and inter-observer reproducibility was found for the up-down paradigm; some variability was seen in normal rats, attributable to extensive testing. Thresholds in a sizable group of neuropathic rats showed insignificant variability over 20 days. After 50 days, 61% still met strict neuropathy criteria, using survival analysis. Threshold measurement using the up-down paradigm, in combination with the neuropathic pain model, represents a powerful tool for analyzing the effects of manipulations of the neuropathic pain state.
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            Osteoarthritis: a disease of the joint as an organ.

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              Lifestyle, Oxidative Stress, and Antioxidants: Back and Forth in the Pathophysiology of Chronic Diseases

              Oxidative stress plays an essential role in the pathogenesis of chronic diseases such as cardiovascular diseases, diabetes, neurodegenerative diseases, and cancer. Long term exposure to increased levels of pro-oxidant factors can cause structural defects at a mitochondrial DNA level, as well as functional alteration of several enzymes and cellular structures leading to aberrations in gene expression. The modern lifestyle associated with processed food, exposure to a wide range of chemicals and lack of exercise plays an important role in oxidative stress induction. However, the use of medicinal plants with antioxidant properties has been exploited for their ability to treat or prevent several human pathologies in which oxidative stress seems to be one of the causes. In this review we discuss the diseases in which oxidative stress is one of the triggers and the plant-derived antioxidant compounds with their mechanisms of antioxidant defenses that can help in the prevention of these diseases. Finally, both the beneficial and detrimental effects of antioxidant molecules that are used to reduce oxidative stress in several human conditions are discussed.
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                Author and article information

                Contributors
                Journal
                Front Nutr
                Front Nutr
                Front. Nutr.
                Frontiers in Nutrition
                Frontiers Media S.A.
                2296-861X
                16 November 2023
                2023
                : 10
                : 1217051
                Affiliations
                [1] 1Molecular Science Lab, National Institute of Immunology (NII) , New Delhi, India
                [2] 2Wellman Center for Photomedicine, Massachusetts General Hospital, Harvard Medical School , Boston, MA, United States
                [3] 3M/s Purobien Lifesciences Ltd , Baddi, Himachal Pradesh, India
                Author notes

                Edited by: Ananth Kumar Kammala, University of Texas Medical Branch at Galveston, United States

                Reviewed by: Sui Kiat Chang, Universiti Tunku Abdul Rahman, Malaysia; Kok Lun Pang, Newcastle University Medicine Malaysia, Malaysia

                *Correspondence: Sarika Gupta, sarika@ 123456nii.ac.in
                Article
                10.3389/fnut.2023.1217051
                10693428
                38045809
                2837152f-eba4-42a7-aa4e-82eec284af3b
                Copyright © 2023 Upadhyay, Kalra, Nilakhe, Aggrawal and Gupta.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 04 May 2023
                : 23 October 2023
                Page count
                Figures: 8, Tables: 1, Equations: 0, References: 66, Pages: 22, Words: 12986
                Funding
                This study received funding support from the National Institute of Immunology (core grant), Department of Biotechnology, New Delhi, India. Subsequently, the formulation details were transferred as an intellectual property right (IPR) to a company called M/s Purobien Lifesciences for commercialization in the nutraceutical category.
                Categories
                Nutrition
                Original Research
                Custom metadata
                Nutrition and Metabolism

                inflammation,monosodium iodoacetate,pro-inflammatory,chemokines,chondroprotective

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