The editorial board of Acupuncture and Herbal Medicine recently convened an academic seminar with a focus on studies regarding the mechanisms mediating acupuncture efficacy and moxibustion action inspired by the 2021 Nobel Prize in Physiology or Medicine. Specifically, Professor Bailong Xiao introduced the Nobel Prize for research on the mechanically activated Piezo ion channel, evaluating the structure of the Piezo channel and its physiological and pathological functions, and proposed a possible role for the Piezo channel in acupuncture mechanical stimulation. Professor Michael Xi Zhu introduced the discovery of the transient receptor potential (TRP) family, reporting that the therapeutic effects of Chinese medicine and acupuncture may be achieved via the TRP family, and that information regarding associations between the meridian and lymphatic systems may have important research and medical value. In addition, Professor Tianle Xu reviewed the history of ion channel research, particularly the physiological and pharmacological effects of non-classical ion channels (eg, the acid sensing ion channel family) and pointed out that the characterization and neural circuits of acupuncture deqi manipulation are important for elucidating the mechanisms of acupuncture actions. Professor Yongming Li similarly proposed that the 2021 Nobel Prize may open the door to disclosing the histological basis of acupuncture and moxibustion and analyzing the main scientific concerns regarding the clinical translation of acupuncture and moxibustion from basic to translational research. Finally, Professor Yi Guo summarized the study progress of the acupoint microenvironment induced by acupuncture over the course of nearly 30 years and put forward the hypothesis that acupuncture may initiate the physical-chemical coupling network by activating ion channel receptors in acupoints via physical and mechanical stimulation. Therefore, we conclude that a primary achievement of the 2021 Nobel Prize in Physiology or Medicine is in helping interpret how acupuncture and moxibustion adjust homeostasis (ie, by activating mechanical and thermal sensation), which is conducive to validating and promoting the clinical efficacy of acupuncture modalities.
Pharmaceutical production is changing from batch production to continuous production, during which granulation is one of the most important unit operations. The quality of mass-produced products is traditionally guaranteed by conducting off-line testing, which cannot meet the demand of continuous production for real-time monitoring of critical process parameters and critical quality attributes (CQAs) of the pharmaceutical granulation technology. Since the U.S. Food and Drug Administration proposed process analytical technology (PAT) in 2004, many PAT tools have been developed to monitor the granulation process and provide information regarding the granulation operation conditions and endpoint determination. In this article, we review the recent research and application of two PAT modes in the granulation process, namely, single CQA and multi-CQA PAT, with the aim to provide references for comprehensively improving the technological level of the pharmaceutical granulation process. Furthermore, the potential applications in traditional Chinese Medicine are discussed.
Gout is a common of inflammatory arthritis and is caused by the deposition of monosodium urate (MSU) crystals as a result of hyperuricemia (HUA). Although HUA is considered to be the main risk factor for gout, only approximately 10% of the individuals with HUA will eventually experience a gout attack. In this review, we first briefly introduce the development of gout and then summarize several possible reasons for its development. Genetic factors play a more prominent role in gout than in other diseases; functional mutations related to urate control and innate immunity components have been found to be associated with gout. Here, we list some of the most prominent genes involved in the pathogenesis of gout. In joints with MSU deposition, mature macrophages may uptake MSU crystals without causing inflammation, and this helps to maintain joints in an asymptomatic state. As an auxiliary inflammation pathway, the ATP-P2X7R-NLRP3 axis may contribute to the amplification of MSU-induced inflammation to affect the development of gout. Finally, this review summarizes the research progress on natural products that can be used in the treatment of HUA and gout.
Objective: Pinellia Tuber, the dried tuber of Pinellia ternata, is widely used in Japanese Kampo medicines and traditional Chinese medicines. The unprocessed Pinellia Tuber is known to cause very strong acrid irritation at oral and laryngopharynx mucosa. Recent studies have shown that the sharp needle-like crystals called raphides, that are composed of calcium oxalate and proteins, are the main causative substances of the irritation. Ginger, the rhizome of Zingiber officinale, has been used in the processing to reduce the acridity of Pinellia Tuber since before the sixth century, however, the mechanisms of reducing acridity have not been scientifically proved yet.
Methods: We developed the raphides denaturation assay (RDA) to quantify the degree of denaturation in the raphides to cause irritation. By their lipophilic characters, the raphides could be extracted in petroleum ether (PE) layer from powdered Pinellia Tuber suspended in water, and the contents of the raphides in PE layer were measured by the absorbance. By this assay, we conducted the activity-guided fractionation from the boiling water extract of ginger to find the ingredients to denature the raphides. We also conducted the gustatory tests to detect the change of the irritation of the denatured raphides.
Results: The treatment of powdered Pinellia Tuber suspension with ginger extract reduced the distribution of raphides in PE layer in RDA in a concentration-dependent manner. The activity-guided fractionation using RDA revealed that oxalic acid was the main active ingredient in ginger extract to denature the raphides of Pinellia Tuber. Oxalic acid reduced the lipophilicity of the raphides in the thermo-, time-, and concentration-dependent manners, and its activity was affected by pH. The treatment of powdered Pinellia Tuber suspension with oxalic acid significantly reduced its acrid irritation in gustatory test in human.
Conclusions: We found that oxalic acid is the main active ingredient in ginger to reduce the acrid irritation of Pinellia Tuber.
Objective: Tribulus terrestris L. (T. terrestris) is a highly valuable traditional Chinese medicine used to treat stroke, inflammation, pulmonary fibrosis, liver cancer, and urolithiasis. To identify the basic substance responsible for the anti-inflammatory effect of TST (total saponins of Tribulus), its chemical composition was systematically studied, and its effect of inhibiting nitric oxide generation and the expression of related inflammatory factors were determined.
Methods: To separate chemical constituents from T. terrestris by column chromatography. Spectroscopic methods, including 1D and 2D nuclear magnetic resonance spectroscopy (NMR) and mass spectrometry (MS) techniques, were used to elucidate the isolated compounds. The anti-inflammatory activities of TST and several compounds were evaluated in vitro.
Results: Fifteen steroidal saponins, including 9 furostanol steroidal saponins (1, 2, 3, 4, 5, 6, 7, 8, and 15) and 6 isospirostanol steroidal saponins (9, 10, 11, 12, 13, and 14), were isolated from T. terrestris. TST significantly decreased the expression of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) in RAW 264.7 cells stimulated by lipopolysaccharides. Compounds 13 and 15 evidently reduced TNF-α expression. Compounds 6, 10, 12, 13, and 15 markedly reduced IL-6 expression.
Conclusions: Compounds 1 was a novel furostanol steroidal saponin, named 26-O-β-D-glucopyranosyl-(25R)-5α-furostan-12-carbonyl-20(22)-en-3β, 26-diol-3-O-{β-D-xylopyranosyl-(1→2)-[β-D-xylopyranosyl-(1→3)]-β-D-glucopyranosyl-(1→4)-[α-L-rhamnopyranosyl-(1→2)]-β-D-galactopyranoside}. Compounds 2 was isolated from the family Zygophyllaceae for the first time, and 5 and 6 were isolated from the Tribulus genus. TST and compounds 6, 10, 12, 13, and 15 exerts anti-inflammatory activity.
Objective: Xiaoyao san (XYS) is a classic traditional Chinese medicinal formula. It has been clinically administered to regulate liver function. However, its mechanisms in glucocorticoid-induced hepatic steatosis are unknown. This study aimed to investigate whether XYS protects against corticosterone (CORT)-induced hepatic steatosis, and to explore its mechanism.Methods: High-fat diet mice induced with hepatic steatosis by 2 mg/kg CORT were administered 2.56 g/kg or 5.12 g/kg XYS daily for 7 weeks. The effects of XYS on hepatic steatosis in mice were evaluated by H&E and Oil Red O staining and by measuring their plasma lipids (triglyceride, total cholesterol, and free fatty acids). The mechanism of XYS against hepatic steatosis was investigated by network pharmacology, immunohistochemistry, western blotting, and gain-of-function/loss-of-function experiments. Results: XYS alleviated CORT-induced steatosis, decreased plasma lipids, and inhibited glucocorticoid receptor (GR) activation in the liver. Network pharmacology data indicated that XYS may have mitigated hepatic steatosis via GR which mediated adipose differentiation-related protein (ADFP). Gain-of-function/loss-of-function experiments in vitro confirmed that GR positively regulated ADFP expression. Conclusions: XYS ameliorated CORT-induced hepatic steatosis by downregulating the GR/ADFP axis and inhibiting lipid metabolism. Our studies implicate that XYS is promising as a therapy for CORT-induced hepatic steatosis, and lay the foundation for designing novel prophylactic and therapeutic strategies on CORT-induced hepatic steatosis.
Objective: Lingzhihuang capsule (LZHC) is a natural product that consists of 10 commonly used medicinal plants, and it is used in traditional Chinese medicine to promote people's overall health. Previously, LZHC was successfully used as adjuvant therapy for treating patients with cancer. However, the chemical constituents of LZHC and their potential biological functions remain unclear. The aim of this study is to investigate the major bioactive compounds in LZHC and predict their pharmacological targets.Methods: The LZHC constituents were putatively identified by ultra-high performance liquid chromatography coupled with time-of-flight mass spectrometry combined with mass spectrometry-based molecular networking. The targets were predicted using SwissTargetPrediction software, and the associated gene ontology and Kyoto encyclopedia of genes and genomes pathways were analyzed using the Database for Annotation, Visualization, and Integrated Discovery. The mass spectrometry-based molecular network and compound-target-pathway network were constructed using Cytoscape 3.8.0 software.Results: We putatively identified 94 compounds of LZHC by mass spectrometry-based molecular networking, including triterpene (the main structural type) and other clusters (ie, flavonoids and organic acids). Our results suggested that multiple pivotal targets were regulated by LZHC, including tumor necrosis factor, nitric oxide synthase 2, glucocorticoid receptor, estrogen receptor, 3-oxo-5-alpha-steroid 4-dehydrogenase 2, prostaglandin e2 receptor ep4 subtype, estrogen receptor beta, phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform, mitogen-activated protein kinase 3, and rac-alpha serine, which are related to signal transduction, positive regulation of transcription from RNA polymerase II promoters, oxidation-reduction processes, inflammatory responses, and other biological processes. Functional annotation of those targets suggested that several signaling pathways may be regulated by LZHC, such as cancer-related proteoglycans, the PI3K-Akt-signaling pathway, and the cAMP-signaling pathway.Conclusions: Our findings reveal the chemical constituents of LZHC and provided scientific support for the efficacy of LZHC in terms of immune regulation, anti-aging, and tumor suppression.