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• BYA inhibited the IL-1β-induced expression of iNOS, COX-2, TNF-α, and IL-6 in vitro. • BYA altered the expression of various proteins, leading to ECM degradation. • BYA suppressed the NF-κB signaling in the IL-1β-induced chondrocytes. • BYA exerted protective effects in OA development in an in vivo DMM model. • In conclusion, BYA may be a potential therapeutic approach for OA. Osteoarthritis (OA) is a chronic musculoskeletal degeneration disease, resulting in severe consequences such as chronic pain and functional disability. Owing to the complex pathology, there are currently available preventative clinical therapies for OA. Several studies have reported the potential anti-inflammatory effects of byakangelicin (BYA), a component of the Angelica dahurica root extract; however, the effects of BYA in OA remain unknown. In this study, we investigated the protective effects of BYA in interleukin (IL)-1β–induced mouse chondrocytes in vitro and on surgical destabilization in a medial meniscus (DMM) mouse OA model in vivo. In vitro , BYA treatment inhibited IL-1β–mediated inducible nitric oxide synthase, cyclooxygenase-2, tumor necrosis factor-alpha, and IL-6 expression. Moreover, BYA promoted the expression of type two collagen and aggrecan but inhibited the expression of thrombospondin motifs 5 and matrix metalloproteinases, leading to degradation of the extracellular matrix. In addition, BYA mechanistically suppressed nuclear factor-kappa B signaling in the IL-1β–induced chondrocytes. The protective effects of BYA in OA development were also observed in vivo using the DMM model. In conclusion, our results highlight BYA as a candidate for OA treatment and prevention. [ABSTRACT FROM AUTHOR]

• Hinokitiol lowered RANKL-induced osteoclast formation and bone resorption in vitro. • Hinokitiol inhibited early activation of the ERK, p38, and JNK–MAPK pathways. • Hinokitiol also suppressed the activity and expression of c‐Jun, c‐Fos, and NFATC1. • Hinokitiol treatment protected against ovariectomy-induced bone loss in vivo. • Hinokitiol has potential as a novel treatment for osteoclast-induced osteoporosis. Osteoporosis is a metabolic bone-loss disease characterized by abnormally excessive osteoclast formation and bone resorption. Identification of natural medicines that can inhibit osteoclastogenesis, bone resorption, and receptor activator of nuclear factor-κB ligand (RANKL)‐induced signaling is necessary for improved treatment of osteoporosis. In this study, hinokitiol, a tropolone-related compound extracted from the heart wood of several cupressaceous plants, was found to inhibit RANKL-induced osteoclast formation and bone resorption in vitro. Hinokitiol inhibited early activation of the ERK, p38, and JNK–MAPK pathways, thereby suppressing the activity and expression of downstream factors (c‐Jun, c‐Fos, and NFATC1). Consistent with the above in vitro findings, hinokitiol treatment protected against ovariectomy-induced bone loss in vivo. Collectively, our results imply that hinokitiol can potentially serve as an effective agent for treating osteoclast-induced osteoporosis. [ABSTRACT FROM AUTHOR]

SSS07 is a rabbit derived humanized anti-human TNF-α antibody. This study aimed to explore the pharmacokinetics, safety, and immunogenicity of SSS07 when administrated subcutaneously in healthy adults. This was a double-blind, dose-escalation study of SSS07 in 71 adults. Dose cohorts were set to 5 mg, 15 mg, 30 mg, 50 mg, 75 mg, and 100 mg. In each dosage group, other than 100 mg, twelve healthy participants were randomly assigned to receive a single dose of SSS07 (n = 10) or placebo (n = 2). Blood samples were taken for pharmacokinetics and immunogenicity analysis. No deaths, serious adverse events or drug-related withdrawals occurred in this trial. No drug limited toxicity appeared. After subcutaneous injection, SSS07 was absorbed slowly with T max ranging from 60 to 264 h but eliminated quickly with a short half-life ranging from 21.69 to 78.4 h (1–3 days). From 5 mg to 100 mg, dose-exposure proportionality analysis found a 90% confidence interval (CI) of β of C max (1.015–1.193), AUC 0-t (1.096–1.263) and AUC 0-∞ (0.999–1.174) partially within the range 0.926–1.074. The plasma concentration of TNF-α decreased significantly post-dose, but a few days later, levels of TNF-α elevated rapidly and exceeded its baseline value. All participants receiving SSS07 were found to be anti-drug antibody positive during the study. A single-dose injection of SSS07 was safe and well-tolerated in healthy adults. Doses of SSS07 from 5 mg to 100 mg could not be regarded as nonlinear, based on dose-exposure proportionality analysis. A high incidence of anti-drug antibodies indicated strong immunogenicity, which may influence the pharmacokinetics profile and interfere with the TNF-α inhibition capability of SSS07. • The rabbit-derived humanized anti-TNF-α antibody, SSS07, was safe in healthy adults. • Immunogenicity might alter the PK profiles and TNF-α binding capability of SSS07. • High doses of SSS07 may induce lower levels of antidrug antibodies compared with small doses. [ABSTRACT FROM AUTHOR]