In Vitro Effects of Low Doses of β-Caryophyllene, Ascorbic Acid and d-Glucosamine on Human Chondrocyte Viability and Inflammation

Abstract

β-caryophyllene (BCP), a plant-derived sesquiterpene, has been reported to have anti-inflammatory and antioxidant effects. The purpose of this study is to evaluate the effects of BCP in combination with ascorbic acid (AA) and d-glucosamine (GlcN) against macrophage-mediated inflammation on in vitro primary human chondrocytes. Changes in cell viability, intracellular ROS generation, gene expression of pro-inflammatory mediators, metalloproteinases (MMPs), collagen type II and aggrecan were analyzed in primary human chondrocytes exposed to the conditioned medium (CM) of activated U937 monocytes and subsequently treated with BCP alone or in combination with AA and GlcN. The CM-induced chondrocyte cytotoxicity was reduced by the presence of low doses of BCP alone or in combination with AA and GlcN. The exposure of cells to CM significantly increased IL-1β, NF-κB1 and MMP-13 expression, but when BCP was added to the inflamed cells, alone or in combination with AA and GlcN, gene transcription for all these molecules was restored to near baseline values. Moreover, chondrocytes increased the expression of collagen type II and aggrecan when stimulated with AA and GlcN alone or in combination with BCP. This study showed the synergistic anti-inflammatory and antioxidative effects of BCP, AA and GlcN at low doses on human chondrocyte cultures treated with the CM of activated U937 cells. Moreover, the combination of the three molecules was able to promote the expression of collagen type II and aggrecan. All together, these data could suggest that BCP, AA and GlcN exert a chondro-protective action.

Potential Anti-Inflammatory and Chondroprotective Effect of Luzula sylvatica

“…In line with that, the extract had no impact on the secretion of IL1β in the supernatants of PBMCs. Yet, other authors reported that sesquiterpenes were able to have a chondroprotective effect by decreasing NFκB expression [27]. As terpenoids were found previously in L. sylvatica [20], a similar effect could have been expected.…”

Hemp Seed Oil in Association with β-Caryophyllene, Myrcene and Ginger Extract as a Nutraceutical Integration in Knee Osteoarthritis: A Double-Blind Prospective Case-Control Study

“…In fact, in 2020, Rao Jiang-Yan et al showed how, through autophagic activation, BCP is able to alleviate cerebral ischemia/reperfusion injury in mice, highlighting its protective role in animal cells and vessels [ 28 ]. Experimental studies showed that BCP reduces pro-inflammatory mediators such as tumor necrosis factor-alfa (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), thus ameliorating chronic pathologies characterized by inflammation and oxidative stress [ 29 , 30 , 31 , 32 ]. In 2012, Ou Ming-Chiu et al recruited 48 women with primary dysmenorrhea with an NRS > 5.…”

A standardized nutraceutical supplement contributes to pain relief, improves quality of life and regulates inflammation in knee osteoarthritis patients; A randomized clinical trial

“…For instance, AA can stimulate anabolic processes as shown in vitro [ 55 , 56 ]. Furthermore, in a most recent in vitro study, the potency of AA to exert synergistic effects together with β-caryophyllene and d -glucosamine was reported by decreasing the expression of inflammatory molecules and increasing the expression of collagen type II and aggrecan [ 57 ]. In our study we used AA as the active comparator since (a) AA is a common vitamin used in OA supplements and (b) patients enrolled in the study could not be treated only with placebo (ethical issues could be risen).…”