Insights into the Action Mechanisms of Traditional Chinese Medicine in Osteoarthritis

Table 1

Summary of the biological effects of TCM on OA.

List	Compounds	Source or TCM	Cell lines	Biological effects of TCM	Ref.
(1)	Astaxanthin	Marine animals and plants	Human OA chondrocytes	↓MMP-1, ↓MMP-3, ↓MMP-13, ↓phosphorylation of p38 MAPK and ERK1/2, ↓NF-κB signaling	[72]
(2)	Astragalin	Rosa agrestis	Human OA chondrocytes	↓iNOS, ↓COX-2, ↓NO, ↓PGE2, ↓NF-κB signaling, ↓MAPK signaling, ↑PPARγ	[20]
(3)	Aucubin	Aucuba japonica⁢; Eucommia ulmoides	Rat chondrocyte	↓MMPs, ↓COX-2, ↓iNOS, ↓NO; ↓NF-κB signaling	[14]
(4)	Baicalein	Scutellaria baicalensis	Rat chondrocyte; Human OA chondrocytes	↓caspase signaling, ↓NO, ↓MMP-3, ↓MMP-13, ↑GAG, ↑type II collagen,; ↓phosphorylation of p38 and ERK	[45, 46, 70]
(5)	Bavachin	Psoralea corylifolia	CHON-002	↓NF-κB signaling	[19]
(6)	Bee venom	Apis mellifera	Mouse chondrocytes	↓MMP-1, ↓MMP-8, ↓NF-κB and AP-1 pathways, ↓phosphorylation of Akt, JNK, and ERK1/2	[73]
(7)	Berberine	Rhizoma coptidis	SW1353,; Rat chondrocyte; Rat in vivo	↑Bcl-xL/Bax ratio, ↓CNN2, ↓αvβ3 integrin, ↓PKCδ, ↓c-Src, ↓iNOS, ↓caspase-3, ↓NO, ↓NF-κB signaling, ↓MAPK signaling, ↑AMPK signaling, ↓MMP-1, ↓MMP-3, ↓MMP-13, ↑TIMP-1, ↑Akt/p70S6K/S6	[33, 46, 47, 57, 67]
(8)	Biochanin A	Red clover	rabbit chondrocyte	↓MMPs, ↑TIMP-1, ↓NF-κB signaling	[60]
(9)	Celastrol	Tripterygium wilfordii Hook F.	Human OA chondrocytes	↓MMP-1, ↓MMP-3, ↓MMP-13, ↓iNOS-2, ↓COX-2	[17]
(10)	Crocin	Crocus sativus L.	Rabbit in vivo and in vitro	↓MMP-1, ↓MMP-3, ↓MMP-13, ↓NF-κB signaling	[62]
(11)	Delphinidin	Pigmented fruits, vegetables	Human OA chondrocytes	↓COX-2, ↓PGE2, ↓NF-κB signaling, ↓phosphorylation of IRAK-	[21]
(12)	EGCG	Camellia sinensis	C57BL/6 mice in vivo, human synovial fibroblasts	↓COX-2, ↓PGE2, ↓IL-8, ↓TNFα, ↓IL-1β, ↓MMP-1, ↓MMP-3, ↓MMP-8, ↓MMP-13, ↓ADAMTS-5, ↓NF-κB signaling, ↓JNK-MAPK signaling, ↑CITED2	[27–31]
(13)	Ferulic acid	Angelica sinensis (Oliv.)	Porcine chondrocytes	↓IL-1β, ↓TNF-α, ↓MMP-1, ↓MMP-13, ↑SOX9	[83]
(14)	Gentiopicroside	Gentiana macrophylla	Rat chondrocyte	↓phosphorylation of p38, ERK, and JNK, ↓MMPs, ↑type II collagen,	[69]
(15)	Ginsenoside Rb1	Ginseng	Rat chondrocyte; Human OA chondrocytes	↑Bcl-xL/Bax ratio, ↓MPT, ↓caspase-3, ↓NO, ↓iNOS, ↓TNFα, ↓IL-1β, ↑collagen type II, ↑SOX9, ↓MMP-1, ↓MMP-13, ↓Notch signaling	[38–40, 81]
(16)	Ginsenoside Rg1, Rg3, Rg5, Rk1, Rf, Rd, Rc, F4	Ginseng	Rat chondrocyte; Human OA chondrocytes	↑Bcl-xL/Bax ratio, ↑TIMP-1, ↓cytochome c, ↓MMP-13, ↓Bax, ↓Bad, ↓p53, ↓COX-2, ↓NF-κB signaling	[41–44]
(17)	Honokiol	Magnolia officinalis	Human OA chondrocytes	↓iNOS, ↓COX-2, ↓NO, ↓PGE2, ↓IL-6, ↓MMP-13, ↓NF-κB signaling	[15]
(18)	Icariin	Epimedium pubescens	Rabbit chondrocytes; SW 1353	↑SOX9, ↑collagen type II, ↑aggrecan, ↓MMP-13, ↓NF-κB signaling, ↓phosphorylations of p38, JNK, β-catenin,	[78–80]
(19)	Monotropein	Morinda officinalis How	Rat chondrocyte	↓MMP-3, ↓MMP-13, ↑COL2A1	[65]
(20)	Morin	Moraceae	Rat in vivo and in vitro	↓phosphorylation of p38 and ERK1/2, ↓MMP-3, ↓MMP-13, ↑TIMP-1	[75]
(21)	Nicotine	Cigarette	Mouseand rat in vivo, Rat chondrocyte	↑PI3K/Akt/Bcl-2 signaling, ↑nAChR, ↓MMP-13, ↑TIMP-1, ↓IGF-1 signaling, ↑PI3K/Akt/p70S6K/S6 signaling,	[56, 57, 66, 101]
(22)	Pinocembrin	Propolis	Human OA chondrocytes	↓MMP-3, ↓MMP-13, ↓NF-κB signaling	[82]
(23)	Piperine	Piper nigrum	Human OA chondrocytes	↓iNOS, ↓COX-2, ↓NO, ↓PGE2, ↓MMPs, ↓NF-κB signaling	[18]
(24)	Protocatechuic acid	Green tea, catechins	Rabbit chondrocytes	↑aggrecan, ↑type II collagen, ↑SOX9	[98]
(25)	Psoralen	Fructus Psoraleae	Rat chondrocyte	↑aggrecan, ↑type II collagen, ↑SOX9	[99]
(26)	Resveratrol	Cranberries, peanuts, red grapes, Polygonum cuspidatum	Rat chondrocyte; Rabbit chondrocytes; Human OA chondrocytes	↑SIRT1, ↑collagen type II, ↓IL-1β, ↓TNFα, ↓PGE2, ↓NO, ↓iNOS, ↓COX-2, ↓NF-κB signaling, ↓TLR4, ↓MyD88, ↓TRAF6, ↓MMP-13, ↓NF-κB and AP-1 signaling, ↑MAPK signaling, ↓HIF-2α	[24–26, 35, 36, 87, 88, 109]
(27)	Rutin	—	Pig in vivo	↓Coll2-1, ↓Fib3-1, ↓Fib3-2, ↓Coll2-1NO2	[91]
(28)	Saponin	Clematis chinensis	Rat in vivo	↓degradation of ECM	[92]
(29)	Schisandrae Fructus	Schisandra chinensis	SW1353	↓MMP-1, ↓MMP-3, ↓MMP-13, ↓COX-2, ↓iNOS, ↓phosphorylation of p38, ERK1/2, and JNK, ↓NF-κB signaling	[74]
(30)	Sinomenine	Sinomenium acutum	rabbit chondrocyte	↓release of GAG, ↓MMP-13, ↓caspase 3, ↑TIMP-1	[64]
(31)	Tetramethylpyrazine	Ligusticum wallichii Franchat	Rabbit chondrocyte	↓ROS, ↓caspase-3, ↓MMP-3, ↓MMP-13, ↓COX-2, ↓iNOS, ↓type X collagen, ↑TIMP-1, ↑type II collagen	[52, 62]
(32)	Tetrandrine	Stephania tetrandra S. Moore	RAW264.7 cell, ATDC5 cells	↓IL-6, ↓IL-1β, ↓TNFα, ↓PGE2, ↓NO, ↓MMPs, ↓NF-κB signaling, ↓β-catenin signaling	[22]; [84]
(33)	TMF	Murraya exotica	Rat chondrocyte	↓EP/cAMP/PKA, ↓β-catenin signaling, ↓PERK, ↓ATF6, and ↓IRE1 signaling	[54, 55]
(34)	Withaferin A	Withania somnifera	Rabbit chondrocytes	↑collagen type II, ↓COX-2, ↓PI3K/Akt, ↓p38, ↓JNK signaling	[37]
(35)	—	Bauhinia championii	Rat chondrocyte	↑Wnt/β-catenin signaling, ↑Frizzled-2, ↑Wnt-4, ↑β-catenin, ↑Cyclin D1, ↓GSK-3β	[96]
(36)	—	Bushen Zhuangjin Decoction	Rat chondrocyte	↓BIP, ↓ATF4, ↓CHOP, ↓caspase-9, ↓caspase-3, ↓Bax, ↑XBP1, ↑Bcl-2; ↑CDK4, ↑CDK6, ↑Cyclin D1, ↑G1/S cell cycle transition	[53]; [94]
(37)	—	Duhuo Jisheng Decoction	Rat chondrocyte	↑Bcl-2, ↓Bax, ↓caspase-3, ↓caspase-9, ↑CDK4, ↑CDK6, ↑Cyclin D1, ↑G1/S cell cycle transition, ↓VEGF, ↓HIF-1α	[50]; [95, 104]
(38)	—	Eucommiaulmoides	Rat in vivo	↓MMP-1, ↓MMP-3, ↓MMP-13, ↓PI3K/Akt signaling	[76, 77]
(39)	—	Fuyuan Decoction	SW1353 cells	↓iNOS, ↓NO,↓NF-κB signaling, ↑phosphorylation of Smad2/3, ↑COL2A1, ↑SOX9	[51, 97]
(40)	—	Guilu Erxian Jiao	Humanin vivo	↑muscle strength, ↓joint pain, ↓Lequesne index scores	[105]
(41)	—	Juanbi capsule	Rabbit in vivo	↓MMP-2, ↓MMP-9	[63]
(42)	—	Murraya exotica	Rat chondrocyte	↓β-catenin, ↓COX-2, ↓TNFα, ↓IL-β	[110]
(43)	—	Phellodendron amurense	Human OA chondrocytes	↑type II collagen, ↑TIMP-1, ↓MMP, ↓p-ERK1/2, JNK, and p38 MAPK,	[68]
(44)	—	Sanmiao formula	Rat chondrocyte; Rat in vivo	↓MMP-3, ↓ADAMTS-4, ↑TIMP-1, ↑TIMP-3	[59]
(45)	—	Tougu Xiaotong	UMR-106	↑Proliferation, ↓cell mortality, ↓inflammatory cytokine	[106]