Chondroprotective Effects of a Standardized Extract (KBH-JP-040) from Kalopanax pictus, Hericium erinaceus, and Astragalus membranaceus in Experimentally Induced In Vitro and In Vivo Osteoarthritis Models

Abstract

The aim of this study was to investigate the chondroprotective effect of a standardized extract (KBH-JP-040) of the Korean traditional herbs Kalopanax pictus Castor-Aralia, Hericium erinaceus (Bull.) Persoon, and Astragalus membranaceus Schischkin on in vivo and in vitro osteoarthritis (OA) models. Cultured rat chondrocytes were pre-treated with KBH-JP-040 (50, 100 and 200 μg/mL) for 1 h, then recombinant human IL-1α (rhIL-1α) for 24 h. For the in vivo model, rabbits (n = 60) were equally divided into experimental groups: normal control (NC), a collagenase-induced OA group, and OA groups treated with KBH-JP-040 (75, 100, and 150 mg/kg body weight) and celecoxib (Cx, 100 mg/kg) orally for 28 days. Treatment with KBH-JP-040 significantly attenuated inflammatory cytokines and matrix metalloproteinases (MMPs), suppressed the expression of IκBα, NF-κB, and JNK/p38 mitogen-activated protein (MAP) kinase, and upregulated aggrecan and collagen type-II expression in rhIL-1α-stimulated chondrocytes. Furthermore, the serum and synovial levels of inflammatory cytokines of rabbits also decreased in the treatment groups when compared with the OA group. Improved magnetic resonance imaging and histopathological findings further confirmed the therapeutic efficacy of KBH-JP-040 against OA. In conclusion, these results indicate that KBH-JP-040 possesses chondroprotective effects, suppressing inflammation and MMPs, and downregulating IκBα, NF-κB, and JNK/p38 MAP kinase-signaling pathways. This might be a potential therapeutic candidate for OA treatment.

Astragalus (Astragalus membranaceus Bunge): botanical, geographical, and historical aspects to pharmaceutical components and beneficial role

“…The Astragalus saponins induced an anti-inflammatory effect by inhibiting LPS-induced NF-κB pathway resulting in decreased expression of iNOS (Wang et al, 2016). In a study using a standardized extract containing A. membranaceus and two other Korean herbs, KBH-JP-040 extract, caused anti-osteoarthritis potential by inhibiting JNK/p38 MAP-kinase pathway and preventing the production of NF-κB, IκBα, matrix metalloproteinase, and inflammatory cytokines (Rahman et al 2018). Astragaloside-IV (100 µM) prevented myocardial remodeling and fibrosis in rat cardiomyocytes [H9C2(2-1)]] cell line through reduction in the activity levels of Sirt1, Bcl-2, miR-34a, as well as increasing superoxide dismutase activity and reduction of lipid peroxidation (Zhu et al 2019).…”

The Effect of the Prethanol Extract of <b><i>Trifolium pratense</i></b> Leaves on Interleukin-1β-Induced Cartilage Matrix Degradation in Primary Rat Chondrocytes

“…Primary chondrocytes were seeded in 6-well culture plates at 1 × 10 6 cells/mL and incubated for 16 h. The chondrocytes were preincubated with various concentrations of 40% PeTP (0.5, 1, and 2 mg/mL) for 1 h and then stimulated with IL-1β (20 ng/mL) for 24 h, using the following reference methods [Hosseinzadeh et al, 2017;Rahman, 2018]. NO accumulation in the culture medium was determined by Griess reagent, as previously described [Lee et al, 2018a].…”

Immune-Enhancing Effects of Co-treatment With Kalopanax pictus Nakai Bark and Nelumbo nucifera Gaertner Leaf Extract in a Cyclophosphamide-Induced Immunosuppressed Rat Model

“…Since plants have beneficial pharmacological effects, low toxicity, and fewer side effects on human health, they have traditionally been used in oriental medicine. Kalopanax pictus Nakai Bark (KP) and Nelumbo nucifera Gaertner leaf (NN) have been shown to have various pharmacological activities, including anti-inflammatory ( 13 – 16 ), anti-nociceptive ( 14 ), anti-diabetic ( 15 , 16 ), and anti-cancer ( 15 – 19 ) effects. The main components of KP and NN have been identified as liriodendrin and kalopanaxaponin ( 20 , 21 ), and flavonoids and alkaloids ( 22 , 23 ), respectively.…”

“…Natural products are often blended to maximize the therapeutic effect. Although the anti-inflammatory effects of KP and NN extracts have been demonstrated in vitro and in vivo ( 13 – 16 ), the effects of KP and NN combination (KPNN) treatment on the immune response are yet to be elucidated. Therefore, we investigated the immune-enhancing effects and synergistic effect of KPNN in macrophages, splenocytes, and an immunosuppressed rat model.…”