Shanghai Institute of Materia Medica (SIMM) was established in 1932 and launched APS, the official journal of Chinese Pharmacological Society in 1980. SIMM is a reputable and comprehensive pharmaceutical research institution with a wide range of disciplines. With each passing decade, SIMM continues to garner outstanding achievements, and recruit the top talents in each field, becoming one of the most innovative drug research facilities in China, leading the way in novel pharmaceutical research. To better understand the research progress of SIMM in the past decade and providing insight into the exciting and innovative drug research and development in China, APS has organized this special issue including reviews and original articles that highlight the contributions of principal investigators from SIMM in various disciplines.

Schematic depicting the role of  trilobatin (TLB) on Alzheimer's disease (AD). TLB, a naturally occurring food additive, rescues cognitive impairment of AD via targeting HMGB1 through activation of SIRT3/SOD2/mtROS signaling pathway, leading to reduced levels of inflammatory factors and oxidative stress. 

Sapidolide A (SA) treats acetaminophen-induced liver injury (AILI) by inhibiting NLRP3 inflammasome activation in macrophages. Acetaminophen (APAP) causes hepatocyte necrosis, which releases DAMPs and induces NLRP3-inflammasome-mediated macrophage pyroptosis. This leads to the secretion of pro-inflammatory factors, such as IL-1β and IL-18, that further recruits immune cells and aggravates liver inflammation, as well as hepatocyte damage. SA acts as an inhibitor of NF-κB signaling, NLRP3 inflammasome activation, and pyroptosis in macrophages, thereby reducing inflammation and protecting against AILI.

This work discovered that depletion of Clk1 significantly suppressed methamphetamine-induced reward behaviors in Clk1+/- mutation mice, which was accompanied by elevated expression of dopamine transporter (DAT).  It was further demonstrated that HIF-1α-mediated change in iron homeostasis is involved in the Clk1 deficiency-altered DAT expression by interrupting its degradation.

Schematic diagram showing how metformin promotes SCI (spinal cord injury) recovery. After SCI, metformin treatment not only reverses the SCI-induced blockade of autophagic flux in microglial cells, but also promotes the transformation of microglial cells from M1 to M2 phenotype polarization, subsequently enhancing the myelin debris clearance, which consequently promotes myelin preservation and nerve repair following SCI.

Bile acids are important mediators for lipid absorption, distribution, and metabolism through activation of bile acid receptor FXR. Disregulation in bile acid homeostasis and FXR function resulted in NASH. The cover art dipicts the role of FXR in bile acid regulation and the FXR structure as the basis for rational drug design for treating NASH, both topics are reviewed by Jiao et al and by Tian et al in pages 1103 and 1120, respectively.

Through computational predictions and successive experimental validations, a few natural products were discovered to potentially block the infection of SARS-CoV-2 by interrupting the binding between the viral spike protein and human receptor ACE2.

Sun Wukong, also known as Qitiandasheng, a character with tremendous magic power and is almost immortal after eating a kind of legendary fruit named "Renshenguo". We thus select Sun Wukong for illustration of the strong anti-heart aging efficacy of Emodin and Kanglexin. Kanglexin displays stronger efficacy than Emodin because of its more potent binding affinity to Parkin.

Proposed mechanism by which orosomucoid (ORM) is involved in adipose tissue fibrosis. ORM1-deficient mice showed significant increases in fat mass and excessive collagen deposition. Exogenous administration of ORM activates adipose tissue AMPK, inhibits TGF-β1 levels, and reduces the expression of collagen and extracellular matrix (ECM) mediators, thus alleviating adipose tissue fibrosis. See the article in pages 367–375.

Benzimidazoles are promising candidates for the treatment of GBM via arresting cell cycle and inducing concurrent apoptotic and pyroptotic cell death. It is of great importance to develop benzimidazoles for combination therapy or as alternative drugs for GBM patients who are resistant or less responsive to temozolomide.