Kartogenin is an activator of the smad4/smad5 pathway, and promotes the selective differentiation of multipotent mesenchymal stem cells into chondrocytes. It is promising agent for treatment of osteoarthritis.

4-hydroxy-2-nonenal (4-HNE or HNE), a very reactive aldehyde derived from lipid peroxidation, is the product and mediator of oxidative stress. It can modulate a number of signaling processes mainly through forming covalent adducts with nucleophilic functional groups in proteins, nucleic acids, and membrane lipids. HNE is mutagenic and genotoxic because it reacts with all four DNA bases but with different efficiency: G >C > A >T. In addition, in the experiments with dogs was shown the pathophysiologic role of HNE in osteoarthritis.

Echinocystic acid (EA) is a pentacyclic triterpene isolated from the fruits of Gleditsia sinensis Lam, has potent antioxidant, anti-inflammatory and anti-tumor properties. Echinocystic acid (EA) inhibit the formation of osteoclast. EA inhibit RANKL-induced NF-κB activation and ERK phosphorylation in BMMs. Echinocystic acid inhibits IL-1β-induced COX-2 and iNOS expression in human osteoarthritis chondrocytes. Echinocystic acid also inhibited TPA-induced myeloperoxidase activity, as well as COX-2, iNOS, TNF-α and IL-1β expressions. Echinocystic acid inhibited NF-κB in TPA-treated mouse ears, as well as in lipopolysaccharide-stimulated peritoneal macrophages. Its potency is comparable with that of dexamethasone. These findings indicate that echinocystic acid may ameliorate inflammatory diseases, such as dermatitis. EA inhibited ACAT and DGAT, with IC50 values of 103 and 139  uM, respectively, and exhibited no significant effect on HMG-CoA reductase activity. The present findings suggest that EA may exert hypolipidemic effect by inhibiting the activity of ACAT and DGAT.

Aucubin is found in common verbena. Aucubin is a monoterpenoid based compound. Aucubin, like all iridoids, has a cyclopentan-[C]-pyran skeleton. Aucubin is found in the leaves of Aucuba japonica (Cornaceae), Eucommia ulmoides (Eucommiaceae), and Plantago asiatic (Plantaginaceae), etc, plants used in traditional Chinese and folk medicine. Aucubin was found to protect against liver damage induced by carbon tetrachloride or alpha-amanitin in mice and rats when 80 mg/kg was dosed intraperitoneally. Aucubin has been shown to exhibit anti-proliferative and apoptotic functions. Aucubin has shown effectiveness as antifungal and suggests its promising potential use as solution for C. albicans biofilm-related infections. Aucubin has a range of biological activities, including anti-inflammatory, anti-microbial, anti-algesic as well as anti-tumor activities.

Taraxasterol is a pentacyclic-triterpene and one of the main active components isolated from Taraxacum officinale. It has been reported to have potent anti-inflammatory properties. The anti-inflammatory effects of taraxasterol against LPS-induced acute lung injury may be due to its ability of inhibition of the NF-κB and MAPK signaling. In addition, taraxasterol protected human chondrocytes by inhibiting MMPs, NO and PGE2 production and therefore could be a useful agent for prevention and treatment of osteoarthritis.

Butein, a plant polyphenol, has been reported to exhibit several important pharmacological effects, such as anti-inflammatory, anti-cancer, anti-oxidant and anti-angiogenic. It was first found in Toxicodendronvernicifluum, a tree widely used as a local food additive and therapeutic supplement in South East Asia. It can also be isolated from the heartwood of Dalbergiaodorifera, the seed of Cyclopiasubternata and the stems of Semecarpusanacardium, as well as many other plants. Butein was shown to be a specific protein tyrosine kinase inhibitor. This compound inhibited tyrosine-specific protein kinase activities of EGF receptor and p60(c-Src). In preclinical settings, it was shown to improve the treatment outcome of several chronic diseases including inflammation, neurological disorders, neoplasms, atherosclerosis, as well as infectious diseases, and most of these actions were accomplished by the inhibition of the transcription factor NF-κB and its downstream targets.

Thiosalicylic acid is an analgesic and anti-inflammatory agent. It is used (in form of sodium salt) to relieve symptoms of acute gout, painful musculoskeletal conditions, osteoarthritis and rheumatic fever. The drug exerts its action by inhibiting prostaglandin synthesis. Thiosalicylic acid usage is associated with the risk of contact dermatitis.

N-Acetylglucosamine (N-acetyl-D-glucosamine, or GlcNAc,) is a monosaccharide and a derivative of glucose. It is part of a biopolymer in the bacterial cell wall, built from alternating units of GlcNAc and N-acetylmuramic acid (MurNAc), cross-linked with oligopeptides at the lactic acid residue of MurNAc. This layered structure is called peptidoglycan (formerly called murein). GlcNAc is the monomeric unit of the polymer chitin, which forms the outer coverings of insects and crustaceans. It is the main component of the radulas of mollusks, the beaks of cephalopods, and a major component of the cell walls of most fungi. It is lnsown, that the breakdown of glycosaminoglycans is an important consequence of inflammation at mucosal surfaces, and inhibition of metalloprotease activity may be effective in treating chronic inflammation. GlcNAc directly incorporates into glycosaminoglycans and glycoproteins, as a substrate for tissue repair mechanisms. It was shown, that GlcNAc was promising substance for treatment of chronic inflammatory bowel disease, with a mode of action which is distinct from conventional treatments. In experiments on rabbits with osteoarthritis, was found chondroprotective effects of aminomonosaccharide glucosamine, but no statistically significant difference was found between study groups. It was also investigated for the treatment of Multiple sclerosis, however, as a drug development target, GlcNAc had significant limitations. GlcNAc has poor membrane permeability, requiring high concentrations for biological effects.

Valdecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, is classified as a nonsteroidal anti-inflammatory drug (NSAID). Valdecoxib was manufactured and marketed under the brand name Bextra. Bextra was indicated for relief of the signs and symptoms of osteoarthritis and adult rheumatoid arthritis. For the treatment of primary dysmenorrhea. But in 2005 FDA requested that Pfizer withdraw Bextra from the American market, because the Agency had concluded that the overall risk versus benefit profile of Bextra was unfavorable. That conclusion was based on the potential increased risk for serious cardiovascular (CV) adverse events, an increased risk of serious skin reactions (e.g., toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme) compared to other NSAIDs, and the fact that Bextra had not been shown to offer any unique advantages over the other available NSAIDs.

Rofecoxib is a nonsteroidal anti-inflammatory drug which selectively inhibits COX-2 and subsequent prostaglandin synthesis. The drug was developed by Merk and approved by FDA in 1999 for relief of signs and symptoms of arthritis, acute pain in adults, and painful menstrual cycles under the name Vioxx. Later on Merck voluntarily withdrawn Vioxx from the market due to safety concerns (high risk of heart attack and stroke).