Chong-Zhi Wang

The rhubarb root and the senna leaf are two commonly used laxative herbs for functional constipation, containing dianthrones and free anthraquinones. As a free anthraquinone, emodin is a crucial constituent isolated from laxative botanicals, and it is particularly abundant in the rhubarb root, a key ingredient in the classic Chinese medicine formula MaZiRenWan (or herbal medicine CDD-2101). This study explored emodin’s anti-malignancy, anti-inflammation, and underlying mechanisms. We examined emodin and other anthraquinones on human colorectal cancer cell proliferation, then used Apc ^Min/ [Formula: see text] mice to assess effects on animal lifespan, intestinal tumor multiplicity, inflammatory cytokines, and adaptive immunity. Results showed MaZiRenWan extract inhibited HCT-116/HT-29 human cancer cells. However, two primary dianthrone sennosides, sennoside A and sennoside B, did not demonstrate such pronounced effects. Three free anthraquinones, emodin, aloe-emodin, and rhein, displayed antiproliferative effects on cancer cells, which were observed to be significantly concentration- and time-dependent, with emodin demonstrating the strongest action. Emodin was found to induce cell cycle arrest during the S-G2/M phases and trigger apoptosis. In vivo, emodin extended Apc ^{Min/[Formula: see text]} mice lifespan, reduced gut tumors, downregulated gut tissue levels of key pro-inflammatory cytokines such as IL-1α, IL-1β, IL-6, IL-17A, IL-8, G-CSF, and GM-CSF; this result was supported by the IL-8 secretion test. Emodin had no inhibitory effect on regulatory Treg cell differentiation, yet it effectively suppressed the Th1 and the Th17 cell differentiation. In conclusion, emodin prevents colorectal cancer via inhibiting cell growth, anti-inflammation, and adaptive immunity modulation, highlighting its potential in inflammation-associated colorectal cancer prevention.

Background Artemisinin (ART) and its derivatives are important antimalaria agents and have received increased attention due to their broad biomedical effects, such as anticancer and anti-inflammation activities. Recently, ruthenium-derived complexes have attracted considerable attention as their anticancer potentials were observed in preclinical and clinical studies. Methods To explore an innovative approach in colorectal cancer (CRC) management, we synthesized ruthenium–dihydroartemisinin complex (D–Ru), a novel metal-based artemisinin derivative molecule, and investigated its anticancer, anti-inflammation, and adaptive immune regulatory properties. Results Compared with its parent compound, ART, D–Ru showed stronger antiproliferative effects on the human CRC cell lines HCT-116 and HT-29. The cancer cell inhibition of D–Ru comprised G1 cell cycle arrest via the downregulation of cyclin A and the induction of apoptosis. ART and D–Ru downregulated the expressions of pro-inflammatory cytokines IL-1β, IL-6, and IL-8. Although ART and D–Ru did not suppress Treg cell differentiation, they significantly inhibited Th1 and Th17 cell differentiation. Conclusions Our results demonstrated that D–Ru, a novel ruthenium complexation of ART, remarkably enhanced its parent compound’s anticancer action, while the anti-inflammatory potential was not compromised. The molecular mechanisms of action of D–Ru include inhibition of cancer cell growth via cell cycle arrest, induction of apoptosis, and anti-inflammation via regulation of adaptive immunity.

Asian ginseng, the root of Panax ginseng C.A. Meyer, occupies a prominent position in the list of best-selling natural products in the world. There are two major types of ginseng roots: white ginseng and red ginseng, each with numerous preparations. White ginseng is prepared by air-drying fresh Asian ginseng roots after harvest. Red ginseng is prepared by steaming roots in controlled conditions using fresh or raw Asian ginseng. Red ginseng is commonly used in Asian countries due to its unique chemical profile, different therapeutic efficacy, and increased stability. Compared with the widespread research on white ginseng, the study of red ginseng is relatively limited. In this paper, after a botanical feature description, the structures of different types of constituents in red ginseng are systematically described, including naturally occurring compounds and those resulting from the steam processing. In red ginseng phytochemical studies, the number of published reports on ginsenosides is significantly higher than that for other constituents. Up to now, 57 ginsenosides have been isolated and characterized in red ginseng. The structural transformation pathways during steaming have been summarized. In comparison with white ginseng, red ginseng also contains other constituents, including polyacetylenes, Maillard reaction products, other types of glycosides, lignans, amino acids, fatty acids, and polysaccharides, which have also been presented. Appropriate analytical methods are necessary for differentiating between unprocessed white ginseng and processed red ginseng. Specific marker compounds and chemical profiles have been used to discriminate red ginseng from white ginseng and adulterated commercial products. Additionally, a brief phytochemical profile comparison has been made between white ginseng and black ginseng, and the latter is another type of processed ginseng prepared from white or red ginseng by steaming several times. In conclusion, to ensure the safe and effective use of red ginseng, phytochemical and analytical studies of its constituents are necessary and even crucial.

Background and Objective: Cancer is a major public health problem in the world, and it dramatically affects the life expectancy of patients and their quality of life. Natural products from botanicals could be beneficial in the prevention or treatment of a variety of cancers. Saffron (the extract of Crocus sativus) includes its major constituent, crocin, have been used as a folk medicine for a long time, and they have shown obvious cancer chemoprevention potential. The objectives of this review are to present the progress of research on the effects of saffron and crocin in cancer management and the underlying mechanisms of action. Methods: We searched publications in the English language, published between January 1, 1980 and September 30, 2022, of saffron and crocin on cancer through several search engines, i.e., PubMed, SciFinder and Web of Science. Key Content and Findings: In this article, we first summarize the phytochemical studies of this botanical. Then, we present the anticancer effects of saffron and crocin on different human cancer cells. Saffron and crocin showed obvious antiproliferative effects on human cancer cell lines, including colorectal cancer, breast cancer, lung cancer, prostate cancer, cervical cancer, leukemia, glioblastoma and rhabdomyosarcoma. Finally, the anticancer-related mechanisms of action are summarized, including cell cycle arrest at G0/G1 or G2/M phases, induction of caspase-dependent apoptosis, signaling pathway-linked tumor metabolism regulation, and adaptive immunity regulated inflammation of host immune responses. Conclusions: Previous studies related to saffron and crocin in cancer management have been reviewed and reported results have been analyzed. Clinical data suggest that saffron and crocin have beneficial effects to improve quality of life in cancer patients. Thus, saffron and crocin can be considered promising candidates for future clinical cancer studies.

Background Artemisinin (ART) is an anti-malaria natural compound with a moderate anticancer action. As a metabolite of ART, dihydroartemisinin (DHA) may have stronger anti-colorectal cancer (CRC) bioactivities. However, the effects of DHA and ART on CRC chemoprevention, including adaptive immune regulation, have not been systematically evaluated and compared. Methods Coupled with a newly-established HPLC analytical method, enteric microbiome biotransformation was conducted to identify if the DHA is a gut microbial metabolite of ART. The anti-CRC potential of these compounds was compared using two different human CRC cell lines for cell cycle arrest, apoptotic induction, and anti-inflammation activities. Naive CD4⁺ T cells were also obtained for testing the compounds on the differentiation of Treg, Th1 and Th17. Results Using compound extraction and analytical methods, we observed for the first time that ART completely converted into its metabolites by gut microbiome within 24 h, but no DHA was detected. Although ART did not obviously influence cancer cell growth in the concentration tested, DHA very significantly inhibited the cancer cell growth at relatively low concentrations. DHA included G2/M cell cycle arrest via upregulation of cyclin A and apoptosis. Both ART and DHA downregulated the pro-inflammatory cytokine expression. The DHA significantly promoted Treg cell proliferation, while both ART and DHA inhibited Th1 and Th17 cell differentiation. Conclusions As a metabolite of ART, DHA possessed stronger anti-CRC activities. The DHA significantly inhibited cell growth via cell cycle arrest, apoptosis induction and anti-inflammation actions. The adaptive immune regulation is a related mechanism of actions for the observed effects.

Oplopanax elatus (Nakai) Nakai, in the Araliaceae family, has been used in traditional Chinese medicine (TCM) to treat diseases as an adaptogen for thousands of years. This study established an ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF/MS) method to identify chemical components and biotransformation metabolites of root bark extract from O. elatus. A total of 18 compounds were characterized in O. elatus extract, and 62 metabolites by human intestinal microbiota were detected. Two polyynes, falcarindiol and oplopandiol were recognized as the main components of O. elatus, whose metabolites are further illustrated. Several metabolic pathways were proposed to generate the detected metabolites, including methylation, hydrogenation, demethylation, dehydroxylation, and hydroxylation. These findings indicated that intestinal microbiota might play an essential role in mediating the bioactivity of O. elatus.

It is of great significance for the construction and operation of high head pumped storage power station, high dam project and deep tunnel project to master the seepage characteristics and laws of rock mass shear fracture. In this paper, the seepage characteristics of marble shear fractures are summarized as follows. (1) In the radial seepage test, the seepage process conforms to darcy’s law, and there is a linear relationship between head pressure and flow. (2) The characteristics of local tensile failure in the cracks generated under low normal force during the shear process hinder the seepage. (3) The normal force has a significant influence on the fracture seepage. In the process of the normal force increasing from 36kN to 48kN, the seepage characteristics show a sudden change, and the contact form of the shear fracture surface changes, indicating that part of the seepage channel in this stage appears a closed phenomenon with the increase of the normal force, and a large area of closure is formed in the fracture.