Ginsenoside-Rg5 treatment inhibits apoptosis of chondrocytes and degradation of cartilage matrix in a rat model of osteoarthritis

Abstract

Abstract. This study investigated the effect of ginsenoside-Rg5 on the degradation of articular cartilage in osteoarthritis rat model and on induction of chondrocyte apoptosis. Osteoarthritis rat model was prepared by ligament transection and medial meniscus resection. The rats were then treated with different doses (1, 2, 5, 10 and 15 µM) of ginsenoside-Rg5 for 48 h. The results from histopathological analysis revealed a significant (P=0.005) prevention of cartilage degradation in OA rat model by ginsenoside-Rg5 treatment at 15 µM. Ginsenoside-Rg5 treatment prevented the disintegration of synovial membrane to a significant (P=0.005) extent. The proportion of apoptotic cells in the knee joints was reduced to 7% by ginsenoside-Rg5 treatment after one month compared to the control. Treatment of the rats with ginsenoside-Rg5 caused increase in the levels of proteoglycan, collagen and type II collagen by 5-, 3-and 4-fold compared to the control group. Immunohistochemistry revealed that the level of MMP-13 was reduced to 45% and that of TIMP-1 was increased by 67% on treatment with ginsenoside-Rg5. The levels of interleukin-1β, tumor necrosis factor-α, nitric oxide and inducible nitric oxide synthetase were reduced by 67, 54, 32 ad 49%, respectively after one month of treatment with 15 mg/kg dose of ginsenoside-Rg5. The expression was increased to 67 and 52% for BMP-2 and TGF-β1, respectively on treatment with ginsenoside-Rg5. Thus ginsenoside-Rg5 prevents cartilage degradation in the OA rats and inhibits cartilage apoptosis, therefore it can be used for osteoarthritis treatment. IntroductionOsteoarthritis (OA) is one of the commonly observed diseases of joints caused by the disintegration of cartilage matrix and death of chondrocytes (1). There is always an equilibrium maintained by extracellular cartilage matrix between the formation and loss of chondrocytes (2,3). Loss of chondrocytes is a limiting factor for the formation of extracellular cartilage matrix which subsequently leads to the development of osteoarthritis (4). Many factors such as proteoglycan and collagen (type II) are involved in the regulation of normal functioning of chondrocytes (5). Studies have revealed that chondrocyte loss and extracellular matrix degradation involve several factors including, generation of peroxide radicals, TNF-α and interleukins (6,7). All these factors initiate inflammatory reactions leading to chondrocyte apoptosis (8). Expression of interleukin-1β is responsible for the production of inhibitors of metalloproteinase (TIMPs) leading to the inhibition of matrix metalloproteinase (MMP) generation and subsequent chondrocyte death and OA (9-11).Traditional Chinese medicine (TCM) involves the use of various herbs as well as dietary ingredients for several disorders depending upon the type of the syndrome (12). Numerous studies have been performed to demonstrate the chemotherapeutic potential of TCM against various types of cancers (13). Ginseng has a long traditional medicinal importance for the treatment of cancers, stress and...

Ameliorative effects of ginseng and ginsenosides on rheumatic diseases

“…In addition, Zhang investigated the effect of ginsenoside Rg5 (G-Rg5) on the degradation of articular cartilage in an OA rat model prepared by ligament transection and medial meniscus resection. Histopathological analysis showed that G-Rg5 significantly alleviated OA symptoms by preventing cartilage degradation, synovial membrane disintegration, and apoptotic cell death in the knee joints in ligament transection and medial meniscus resection OA rats [55]. An in vitro study revealed that G-Rg5 increased proteoglycan, collagen, and bone morphogenetic protein 2 levels and decreased MMP-13, IL-1β, TNF-α, nitric oxide, and inducible nitric oxide synthase levels in the chondrocytes of OA rats [55].…”

miRNA‑27a regulates arthritis via PPARγ in�vivo and in�vitro

“…In the process of OA development, matrix degradation and severe damage is often accompanied by excessive apoptosis of cartilage cells (20). Cell apoptosis, also known as programmed death, refers to the physiological process that nucleated cells trigger programmed cell death under the regulation of gene, which causes the natural death of cells and automatical removal of the non-functional, damaged and senescent cells (21). There is a small amount of apoptosis in the normal cartilage tissue, which is usually confined to the surface of cartilage tissue (22).…”

Recent advance in treatment of osteoarthritis by bioactive components from herbal medicine

“…In OA chondrocytes, resveratrol may reverse the decrease in the levels of type II collagen, aggrecan, and glycosaminoglycan by regulating silent information regulator 2 type 1, hypoxia-inducible factor-2α, and MMPs expression [24,62,63,77]. Curcumin [28], naringin [42], icariin [16,78,79], berberine [68,69], sinomenine [72], tetramethylpyrazine [13,70,80], astragaloside IV [81], halofuginone [82], puerarin [83], quercetin [84], celastrol [54,85], harpagoside [32], ferulic acid [55], shikonin, acetylshikonin [86], ginsenoside Rb1 [76,87], cinnamophilin [30], honokiol [50], 2, 3, 5, 4′-tetrahydroxystilbene-2-O-β-d-glucoside [60], geniposide [31], ginsenoside Rg5 [74], cryptotanshinone [29], isofraxidin [33], paeonol [56], crocin [43], coptisine [44], piperine [45], butein [46], licochalcone A [36], tectorigenin [48], theaflavin-3,3′-digallate [59], anemonin [49], gastrodin [51], compound K…”

“…Paeonol alleviates chondrocyte apoptosis by regulating the levels of ROS, bcl-2, and bax [ 56 , 71 ]. Some components (icariin [ 9 ], sinomenine [ 72 ], astragaloside IV [ 73 ], quercetin [ 21 ], shikonin [ 35 ], tectorigenin [ 48 ], gastrodin [ 51 ], and ginsenoside Rg5 [ 74 ]) also exert anti-apoptotic effects on chondrocytes through various mechanisms. The promoting effects of puerarin [ 53 ], psoralen [ 75 ], magnoflorine [ 23 ], and emodin [ 38 ] on proliferation may be also beneficial to reverse cartilage apoptosis.…”

“…In OA chondrocytes, resveratrol may reverse the decrease in the levels of type II collagen, aggrecan, and glycosaminoglycan by regulating silent information regulator 2 type 1, hypoxia-inducible factor-2α, and MMPs expression [ 24 , 62 , 63 , 77 ]. Curcumin [ 28 ], naringin [ 42 ], icariin [ 16 , 78 , 79 ], berberine [ 68 , 69 ], sinomenine [ 72 ], tetramethylpyrazine [ 13 , 70 , 80 ], astragaloside IV [ 81 ], halofuginone [ 82 ], puerarin [ 83 ], quercetin [ 84 ], celastrol [ 54 , 85 ], harpagoside [ 32 ], ferulic acid [ 55 ], shikonin, acetylshikonin [ 86 ], ginsenoside Rb1 [ 76 , 87 ], cinnamophilin [ 30 ], honokiol [ 50 ], 2, 3, 5, 4′-tetrahydroxystilbene-2-O-β-d-glucoside [ 60 ], geniposide [ 31 ], ginsenoside Rg5 [ 74 ], cryptotanshinone [ 29 ], isofraxidin [ 33 ], paeonol [ 56 ], crocin [ 43 ], coptisine [ 44 ], piperine [ 45 ], butein [ 46 ], licochalcone A [ 36 ], tectorigenin [ 48 ], theaflavin-3,3′-digallate [ 59 ], anemonin [ 49 ], gastrodin [ 51 ], compound K [ 37 ], and emodin [ 38 , 39 ] inhibit the expression of MMPs through a variety of pathways, such as IL-1β signaling, NF-κB signaling, AMPK signaling, MAPK signaling, and NO signaling, etc. The inhibition of cartilage catabolic processes by resveratrol [ 24 ], curcumin [ 66 ], and astragaloside IV [ 73 ] may be also related to their regulation on autophagy, activation of which may reduce the severity of OA.…”