The potent anti-inflammatory effect of Guilu Erxian Glue extracts remedy joint pain and ameliorate the progression of osteoarthritis in mice

Abstract

BackgroundOsteoarthritis (OA) is a slow progressing, degenerative disorder of the synovial joints. Guilu Erxian Glue (GEG) is a multi-component Chinese herbal remedy with long-lasting favorable effects on several conditions, including articular pain and muscle strength in elderly men with knee osteoarthritis. The present study aimed to identify the effects of Guilu Erxian Paste (GE-P) and Liquid (GE-L) extracted from Guilu Erxian Glue in anterior cruciate ligament transection (ACLT)-induced osteoarthritis mice, and to compare the effectiveness of different preparations on knee cartilage degeneration during the progression of osteoarthritis.MethodsMale C57BL/6J mice underwent anterior cruciate ligament transection to induce mechanically destabilized osteoarthritis in the right knee. 4 weeks later, the mice were orally treated with PBS, celecoxib (10 mg/kg/day), Guilu Erxian Paste (100 or 300 mg/kg/day), and Guilu Erxian Liquid (100 or 300 mg/kg/day) for 28 consecutive days. Von Frey and open-field tests (OFT) were used to evaluate pain behaviors (mechanical hypersensitivity and locomotor performance). Narrowing of the joint space and osteophyte formation were examined radiographically. Inflammatory cytokine (IL-1β, IL-6, and TNF-α) levels in the articular cartilage were determined by quantitative real-time PCR. Histopathological examinations were conducted to evaluate the severity and extent of the cartilage lesions.ResultsGuilu Erxian Paste and Guilu Erxian Liquid (300 mg/kg/day) were significantly more effective (p < 0.01) than celecoxib (10 mg/kg/day) in decreasing secondary allodynia when compared to the saline-treated group (#p < 0.05). Open-field tests revealed no significant motor dysfunction between the Guilu Erxian Paste- and Guilu Erxian Liquid-treated mice compared to the saline-treated mice. Radiographic findings also confirmed that the administration of Guilu Erxian Paste and Guilu Erxian Liquid (100 and 300 mg/kg/day) significantly and dose-dependently reduced osteolytic lesions and bone spur formation in the anterior cruciate ligament transection-induced osteoarthritis mice when compared to the saline-treated group. Notably, Guilu Erxian Liquid (100 mg/kg/day) treatment significantly reduced the mRNA levels of IL-1β, IL-6, and TNF-α as well as relative the protein expression of IL-1β and TNF-α to the effect of celecoxib. Guilu Erxian Paste and Guilu Erxian Liquid (300 mg/kg/day) markedly attenuated cartilage destruction, surface unevenness, proteoglycan loss, chondrocyte degeneration, and cartilage erosion in the superficial layers (##p < 0.01 and ###p < 0.001 respectively).ConclusionsAs expected, our findings suggest that the anti-inflammatory effects of Guilu Erxian Liquid (GE-L), following marked decrease on both IL-1β and TNF-α during the early course of post-traumatic osteoarthrosis (OA), may be of potential value in the treatment of osteoarthritis.

Effective Dose of Rhizoma Coptidis Extract Granules for Type 2 Diabetes Treatment: A Hospital-Based Retrospective Cohort Study

“…Because type 2 diabetes mellitus frequently co-exists with osteoarthritis ( Veronese et al, 2019 ), Gui-Lu-Er-Xian-Jiao is often given to support the kidney yin and yang for patients with diabetes. This herbal formula can mitigate chondrocyte degeneration, cartilage destruction, and articular pain ( Tsai et al, 2014 ; Chou et al, 2018 ). The current study identified high-dose RCEG and other drugs that are often co-prescribed with it for type 2 diabetes.…”

Unraveling Natural Products’ Role in Osteoarthritis Management—An Overview

“…In the in vivo setting of anterior cruciate ligament transection (ACLT)-induced OA, the effects of a 28-days intervention with GE in the form of either paste or liquid were evaluated in two treatment doses (100 mg/kg/day or 300 mg/kg/day) [42] against phosphate-buffered saline and celecoxib (10 mg/kg/day). Notably, the intervention with the liquid mixture formulation in the minimum dose was able to considerably lessen the mRNA levels of IL-1β, IL-6, and TNF-α, as well as the protein expression of IL-1β and TNF-α, compared to either formulation at high dose and celecoxib [44]. Both formulations presented a notable and dose-dependent reduction of osteolytic lesions, cartilage erosion, and bone spur formation in addition to reductions observed in proteoglycan, chondrocyte, and cartilage damage [44].…”

“…Notably, the intervention with the liquid mixture formulation in the minimum dose was able to considerably lessen the mRNA levels of IL-1β, IL-6, and TNF-α, as well as the protein expression of IL-1β and TNF-α, compared to either formulation at high dose and celecoxib [44]. Both formulations presented a notable and dose-dependent reduction of osteolytic lesions, cartilage erosion, and bone spur formation in addition to reductions observed in proteoglycan, chondrocyte, and cartilage damage [44]. Although the formulations of this mixture presented chondroprotective properties with anti-inflammatory characteristics, the evidence supporting those allocations remain inconclusive.…”

“…There is a growing interest in an herbal mixture that originated in Chinese tradition with reported useful assets in the treatment of some conditions. In particular terms, guilu erxian (GE) glue has been under investigation for its therapeutic potential against joint pain, muscle strength, and disease progression within the context of knee OA, in addition to bone marrow injury and osteoporosis, mostly in the cellular level [42][43][44][45]. For the purposes of this review, we presented the findings of a 2018 study by Chou et al, who evaluated two formulations extracted from GE glue, namely, GE paste and GE liquid in male-induced osteoarthritic mice [44], and reports of a 2014 clinical trial in a population of elderly men with knee OA, which have been presented in the respected segment of the review [45].…”

“…In particular terms, guilu erxian (GE) glue has been under investigation for its therapeutic potential against joint pain, muscle strength, and disease progression within the context of knee OA, in addition to bone marrow injury and osteoporosis, mostly in the cellular level [42][43][44][45]. For the purposes of this review, we presented the findings of a 2018 study by Chou et al, who evaluated two formulations extracted from GE glue, namely, GE paste and GE liquid in male-induced osteoarthritic mice [44], and reports of a 2014 clinical trial in a population of elderly men with knee OA, which have been presented in the respected segment of the review [45]. In the in vivo setting of anterior cruciate ligament transection (ACLT)-induced OA, the effects of a 28-days intervention with GE in the form of either paste or liquid were evaluated in two treatment doses (100 mg/kg/day or 300 mg/kg/day) [42] against phosphate-buffered saline and celecoxib (10 mg/kg/day).…”