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Harpagophytum procumbens Root Extract Mediates Anti-Inflammatory Effects in Osteoarthritis Synoviocytes through CB2 Activation.

ABSTRACT: The endocannabinoid system is involved in the nociceptive and anti-inflammatory pathways, and a lowered expression of CB2 receptors has been associated with inflammatory conditions, such as osteoarthritis (OA). This suggests that CB2 modulators could be novel therapeutic tools to treat OA. In the present study, the involvement of Harpagophytum procumbens root extract, a common ingredient of nutraceuticals used to treat joint disorders, in CB2 modulation has been evaluated. Moreover, to clarify the effects of the pure single components, the bioactive constituent, harpagoside, and the main volatile compounds were studied alone or in a reconstituted mixture. Human fibroblast-like synoviocytes, extracted by joints of patients, who underwent a total knee replacement, were treated with an H. procumbens root extract dissolved in DMSO (HPE_DMSO). The effectiveness of HPE_DMSO to affect CB2 pathways was studied by analyzing the modulation of cAMP, the activation of PKA and ERK MAP kinase, and the modulation of MMP-13 production. HPE_DMSO was able to inhibit the cAMP production and MAP kinase activation and to down-regulate the MMP-13 production. Pure compounds were less effective than the whole phytocomplex, thus suggesting the involvement of synergistic interactions. Present findings encourage further mechanistic studies and support the scientific basis of the use of H. procumbens in joint disorders.

SUBMITTER: Mariano A

PROVIDER: S-EPMC9026917 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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<i>Harpagophytum procumbens</i> Root Extract Mediates Anti-Inflammatory Effects in Osteoarthritis Synoviocytes through CB2 Activation.

Mariano Alessia A Bigioni Irene I Mattioli Roberto R Di Sotto Antonella A Leopizzi Martina M Garzoli Stefania S Mariani Pier Francesco PF Dalla Vedova Pietro P Ammendola Sergio S Scotto d'Abusco Anna A

Pharmaceuticals (Basel, Switzerland) 20220409 4

The endocannabinoid system is involved in the nociceptive and anti-inflammatory pathways, and a lowered expression of CB2 receptors has been associated with inflammatory conditions, such as osteoarthritis (OA). This suggests that CB2 modulators could be novel therapeutic tools to treat OA. In the present study, the involvement of <i>Harpagophytum procumbens</i> root extract, a common ingredient of nutraceuticals used to treat joint disorders, in CB2 modulation has been evaluated. Moreover, to cl ...[more]

PMID: 35455454

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Project description:BACKGROUND:A variety of medicinal products prepared from secondary tubers of Harpagophytum procumbens subsp. procumbens (Burch.) DC.ex Meisn. (Devil's Claw) and H. zeyheri are marketed in Africa, Europe, the United States, South America and elsewhere, where they are used for inflammatory and musculoskeletal conditions such as arthritis, lower back pain, rheumatism and neuralgia, etc. While clinical studies conducted over the last twenty years support the general safety of such products, infrequent gastrointestinal disturbances (diarrhea, nausea, vomiting, abdominal pain), headache, vertigo and hypersensitivity (allergic) reactions (rash, hives and face swelling) have been documented. Sex-related differences occur in the health conditions for which Devil's Claw products are used, so it is likely that usage is similarly sex-related and so might be side effects and potential toxicities. However toxicologic studies of Devil's Claw products have been conducted primarily with male animals. To address this deficit, we report toxicological studies in female and male rats of several H. procumbens (HP) aqueous-alcohol extracts chemically analyzed by UPLC-MS. METHODS:Female and male Sprague Dawley rats were studied for one and three months in groups differing by consumption of diets without and with HP extracts at a 7-10-fold human equivalent dose (HED). Sera were analyzed for blood chemistry, and heart, liver, lung, kidney, stomach, and small and large intestine tissues were examined for histopathology. Treatment group differences for blood chemistry were analyzed by ANOVA with Dunnett's test and significant group differences for endpoints with marginal distributional properties were verified using the Kruskal-Wallis test. Group differences for histopathology were tested using Chi Square analysis. RESULTS:Significant group by sex-related differences in blood chemistry were detected in both studies. Additionally, several sex-related differences occurred between the studies. However, significant histopathology effects associated with the consumption of the extracts were not detected. CONCLUSION:Toxicologic analysis of Devil's Claw extracts cause significant sex-related effects in blood chemistry. However, in our judgement, none of the observed effects suggest serious toxicity at these doses and durations. Subsequent toxicologic and clinical studies of H. procumbens and other medicines with similar properties should explore in greater detail the basis and consequences of potential sex-related effects.

Project description:Background Pain and inflammation are the major devastating health problems commonly treated with traditional medicinal plants in Ethiopia. Echinops kebericho M. (Asteraceae) is the one which is frequently used to treat pain and inflammation by traditional healers in Ethiopian folk medicine. However, the plant has not been scientifically evaluated for its traditionally claimed use. The present study aimed at the investigation of analgesic and anti-inflammatory activities of 80% methanol root extract of Echinops kebericho M. in mice model. Methods Successive maceration was used as a method of extraction using solvents of increasing polarity: methanol and water. After extraction of the roots with 80% hydro methanol, the crude extract was evaluated for its peripheral and central analgesic activities using acetic acid-induced writhing test and hot plate method, respectively, while its anti-inflammatory activity was evaluated using carrageenan- and formalin-induced paw edema. The extract was evaluated at 100, 200 and 400 mg/kg doses. The positive control groups were treated with ASA 150 mg/kg for writhing test, morphine 10 mg/kg for hot plat method, indomethacin 25 mg/kg and diclofenac 10 mg/kg for paw edema tests and vehicle, distilled water (10 mL/kg) treated mice were assigned as negative controls. All treatment administrations were performed orally. Results E. kebericho extract at all test doses showed statistically significant antinociceptive activity in both chemicals-induced peripheral and thermal-induced central pain in a dose dependent manner (p < 0.01 and p < 0.001). The greater analgesic activity was observed by the maximum dose of the extract (400 mg/kg) in both acetic acids-induced writhing test (57.84%) and hot plate method (69.40%). The effect of the extract was also statistically significant (p < 0.01 and p < 0.001) in both carrageenan and formalin-induced paw edema in dose dependent manner. Greater edema inhibition was observed by the highest dose (400 mg/kg) in both observations with the respective percentage values of 70.00% and 79.87%, respectively. Conclusion In general, the data obtained from the present study elucidated that the extract possessed a significant analgesic and anti-inflammatory activities and recommended for further studies.

Dataset Information

Harpagophytum procumbens Root Extract Mediates Anti-Inflammatory Effects in Osteoarthritis Synoviocytes through CB2 Activation.

Publications

<i>Harpagophytum procumbens</i> Root Extract Mediates Anti-Inflammatory Effects in Osteoarthritis Synoviocytes through CB2 Activation.

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