Discovery of a Covalent Inhibitor of Pro-Caspase-1 Zymogen Blocking NLRP3 Inflammasome Activation and Pyroptosis.

Caspase-1 plays a central role in innate immunity, as its activation by inflammasomes induces the production of proinflammatory cytokines and pyroptosis. However, specific inhibition of the enzymatic activity of this protease is not effective in suppressing inflammation, owing to its enzyme-independent function. Herein, we identified a cyclohexenyl isothiocyanate compound () that potently inhibited caspase-1 activity and suppressed the assembly and activation of the NLRP3 inflammasome and gasdermin-D-mediated pyroptosis.

Luteolin and its analog luteolin-7-methylether from Leonurus japonicus Houtt suppress aromatase-mediated estrogen biosynthesis to alleviate polycystic ovary syndrome by the inhibition of tumor progression locus 2.

Ethnopharmacological Relevance: Leonurus japonicus Houtt (L. japonicus, Chinese motherwort), known as Yi Mu Cao which means "good for women", has long been widely used in China and other Asian countries to alleviate gynecological disorders, often characterized by estrogen dysregulation. It has been used for the treatment of polycystic ovary syndrome (PCOS), a common endocrine disorder in women but the underlying mechanism remains unknown.

Isoprenylated Flavonoids and 2-Arylbenzofurans from the Root Bark of L. and Their Cytotoxic Activity against HGC27 Cancer Cells.

Three new compounds (, , and ), together with 32 known ones, were isolated from the root bark of L. using various chromatographic methods. The structures of the undescribed compounds were elucidated based on 1D, 2D NMR, and HRESIMS dataanalysis, while the known ones were identified by comparison of their spectroscopic data with those reported in the literature.

New Monoterpene Glycoside Paeoniflorin Derivatives as NO and IL-1 Inhibitors: Synthesis and Biological Evaluation.

Several monoterpene glycoside compounds were extracted from Pall. Among them, paeoniflorin, a water-soluble monoterpene glycoside found in the root of Pall, exhibits excellent antioxidant pharmacological functions. Initially, Sc(CFSO) was employed as the catalyst for paeoniflorin's dehydration and rearrangement reactions with alcohols.

Separation and identification of terpene-conjugated curcuminoids based on liquid chromatography-tandem mass spectrometry and their in vitro anti-inflammatory activities.

Terpene-conjugated curcuminoids are conjugates of curcuminoids and bisabolanes in the rhizomes of Curcuma longa L. The fragmentation pathways of known three terpene-conjugated curcuminoids (bisabolocurcumin-ether, bisabocurcumin, and demethoxybisabolocurcumin ether) and curcumin, demethoxycurcumin, and bisdemethoxycurcumin were investigated using high-performance liquid chromatography-electrospray ionization tandem mass spectrometry in negative mode to rapidly search and discover similar unknown compounds of the acetone fraction of turmeric. Subsequently, compounds 1-3 were founded in the acetone fraction based on molecular weight and above fragmentation pathways (the characteristic fragment ions, the most and second most abundant fragment ions produced in MS spectra).

A small molecule inhibitor of caspase-1 inhibits NLRP3 inflammasome activation and pyroptosis to alleviate gouty inflammation.

Caspase-1 is an integral regulator of innate immunity, which plays a key role in inflammasome activation and the release of pro-inflammatory cytokines. The development of novel non-peptidic small molecule caspase-1 inhibitors is an important strategy for antagonizing excessively activated caspase-1 induced by inflammatory diseases, including gouty arthritis. In the present study, we identified 63 caspase-1 inhibitors, with different structures and potencies, from bioactive compound libraries.

Inhibition of Phosphodiesterase 5 Promotes the Aromatase-Mediated Estrogen Biosynthesis in Osteoblastic Cells by Activation of cGMP/PKG/SHP2 Pathway.

Mechanical stimulation induces bone growth and remodeling by the secondary messenger, cyclic guanosine 3', 5'-monophosphate (cGMP), in osteoblasts. However, the role of cGMP in the regulation of estrogen biosynthesis, whose deficiency is a major cause of osteoporosis, remains unclear. Here, we found that the prenylated flavonoids, 3--methoxymethyl-7--benzylicaritin (13), 7--benzylicaritin (14), and 4'--methyl-8-isopentylkaempferol (15), which were synthesized using icariin analogs, promoted estrogen biosynthesis in osteoblastic UMR106 cells, with calculated EC values of 1.

A Comparative Study on 5hmC Targeting Regulation of Neurons in AD Mice by Several Natural Compounds.

A series of studies have confirmed that DNA methylation disorder (5mC/5hmC) is closely related to the occurrence and development of some diseases, such as Alzheimer's disease (AD). This study aims at discovering natural compounds that could adjust and control 5-hydroxymethylcytosine (5hmC) levels and improve Alzheimer's disease (AD) neuronal status. Cordycepin and cordycepic acid were selected as research materials, with resveratrol as positive control.

Comprehension of the unique characteristics of traditional Chinese medicine.

Traditional Chinese Medicine (TCM) has made great contributions to human history, especially in China, as has been recorded for thousands of years. The characteristics of TCM in both theory and practice make it different from Conventional Western Medicine (CWM). The characteristics of TCM include phenomenological, philosophical, and methodological aspects.

[Exploration and analysis of theories of five phases, eight trigrams and four elements].

The theory of five phases is significantly different from that of eight trigrams of I Ching (Book of Changes): the eight trigrams represent the materials or phenomena in the nature, whereas five phases put "metal" created by human activities into nature, which organically incorporate the human activities and all the things in the nature and promote the formation of holistic concept of heaven and human being. Without the attendance of man, earth can't generate metal, metal can't restrict wood, and metal can't generate water. So, it can be concluded that the five phases is the improved eight trigrams.

[Historic significance of Hua Tuo's theory of "Six parts" and "Three methods" in cold pathogenic diseases].

In the end of the Eastern Han dynasty, Hua Tuo and Zhang Zhongjing explored deeply and separately the diagnostic and therapeutic principles of cold pathogenic diseases, though they didn't know each other. This was not only because of their excelsior spirit, but also showed the severity of cold pathogenic diseases at that time. The doctors in past dynasties researched and inherited the achievements of Zhongjing's Shang han lun (Treatise on Cold Pathogenic Diseases).