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 (HPEDMSO). The effectiveness of HPEDMSO 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. HPEDMSO 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.

Sorafenib Chemosensitization by Caryophyllane Sesquiterpenes in Liver, Biliary, and Pancreatic Cancer Cells: The Role of STAT3/ABC Transporter Axis

“…Synergistic effects of β-caryophyllene oxide towards sorafenib were also confirmed in a xenograft model of liver cancer [20]. More recently, we reported the potentiating effects of caryophyllane sesquiterpenes towards cannabidiol and harpagoside in hemp and devil's claw extracts, respectively [18,22].…”

“…A number of natural substances have been found to be able to synergize in vitro anticancer drugs and to resensitize cancer cells, acting as chemosensitizers [16]. Among them, β-caryophyllene and β-caryophyllene oxide, two natural sesquiterpenes with a typical caryophyllane skeleton, widely occurring in plants, especially in essential oils (e.g., clove oil, apple mint oil, and hemp essential oil), seeds (e.g., Piper nigrum L.) and rhizomes (Harpagophytum procumbens DC), were shown to possess promising chemosensitizing properties, along with pleiotropic pharmacological activities, including antioxidant, antinflammatory, genoprotective, neuroprotective, and chemopreventive ones, along with a safe toxicity profile [15,17,18]. Moreover, they were found to be able to modulate multiple cascades involved in oxidative stress, inflammation, and cell survival, such as PI3K/Akt/mTOR/S6K1, NF-kB and STAT3 [15].…”

Role of Rosehip, Devil’s claw, and Boswellia serrata in osteoarthritis: molecular and clinical perspectives

“…It has been shown to mediate anti-Inflammatory effects in Osteoarthritis synoviocytes through cannabinoid type 2 (CB2) Activation. Harpagophytum procumbens is able to inhibit the cAMP production and mitogen-activated protein (MAP) kinase activation and to down-regulate the matrix metalloproteinase (MMP-13) production which is the hallmark of osteoarthritis [21] .…”

The Nutraceuticals as Modern Key to Achieve Erythrocyte Oxidative Stress Fighting in Osteoarthritis

“…Moreover, the agonism of some HPE components has been shown on endocannabinoid (CB) receptors, mainly involved in anti-nociceptive transmission. Several studies have highlighted the up-regulation of CB2 following HPE treatment in vitro [ 74 , 75 ]; while in Farpour et al in vivo study, pain reduction following HPE administration was demonstrated [ 76 ]. Its in vitro and in vivo activity is due to the major chemical constituents such as iridoid glycosides (primarily harpagoside, harpagide, and procumbide), triterpenoids, phytosterols (primarily β-sitosterol) and flavonoids such as luteolin and kaempferol [ 77 ].…”

“…Harpagoside, harpagide, and procumbide, found in the tubers of the plant, appear to be the most therapeutically important constituents. Whole-plant extracts appear to have a better therapeutic effect than those prepared from isolated parts [ 71 , 75 ].…”