Uncovering the key pharmacodynamic material basis and possible molecular mechanism of Xiaoke formulation improve insulin resistant through a comprehensive investigation.

ETHNOPHARMACOLOGICAL RELEVANCE: Xiaoke formulation (XKF) has been utilized in clinical practice for decades in China as a treatment option for mild to moderate type 2 diabetes. However, there is still a need for systematic research to uncover the key pharmacodynamic material basis and mechanism of XKF. AIM OF THE STUDY: Aim of to investigate the distribution and metabolism of XKF in normal and insulin resistant (IR) mice were different, and elucidate its key pharmacodynamic material basis and mechanism of action. MATERIALS AND METHODS: Ultra performance liquid chromatography/time of flight mass spectrometry technology was employed to investigate the differences in XKF absorption, distribution, and metabolism between normal and IR mice across blood, liver, feces, and urine samples. Further, network pharmacology was used to predict target proteins and their associated signaling pathways. Then, molecular docking was utilized to validate the activity of key pharmacodynamic components and targets. Finally, IR HepG2 cells were used to detect the glucose consumption under the action of key pharmacodynamic material basis. In addition, the expression of phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT) and phospho-protein kinase B (p-AKT) was determined using western blotting. RESULTS: The study demonstrates significant distinctions in plasma and liver number and abundance of alkaloids, organic acids, flavonoids, iridoids and saponins between normal and IR mice when XKF was administered. Further analysis has shown that the representative components of XKF, including berberine, chlorogenic acid, calycosin, swertiamarin and astragaloside IV have significantly different metabolic pathways in plasma and liver. Prototypes and metabolites of these components were rarely detected in the urine and feces of mice. According to the network pharmacological analysis, these differential components are predicted to improve IR by targeting key factors such as SRC, JUN, HRAS, NOS3, FGF2, etc. Additionally, the signaling pathways involved in this process include PI3K-AKT pathway, GnRH signaling pathway, and T cell receptor signaling pathway. In addition, in vitro experiments indicate that berberine and its metabolites (berberine and demethyleneberine), chlorogenic acid and its metabolites (3-O-ferulic quinic acid and 5-O-ferulic quinic acid), calycosin and swertiamarin could improve IR in IR-HepG2 cells by elevating the expression of PI3K and AKT, leading to an increase in glucose consumption. CONCLUSION: The key pharmacodynamic material basis of XKF, such as berberine and its metabolites (berberrubine and demethyleneberberine), chlorogenic acid and its metabolites (3-O-feruloylquinic acid and 5-O-feruloylquinic acid), calycosin and swertiamarin influence the glucose metabolism disorder of IR-HepG2 cells by regulating the PI3K/AKT signalling pathway, leading to an improvement in IR.

ß-Elemene in zedoary turmeric oil injection induces dyspnea by binding to hemoglobin and upregulating HIF-1α.

ETHNOPHARMACOLOGICAL RELEVANCE: Zedoary turmeric oil injection (ZTOI) extracted from the rhizome extract of Curcuma phaeocaulis Valeton, Curcuma wenyujin Y. H. Chen et C. Ling or Curcuma kwangsiensis S. G. Lee et C. F. Liang, is widely used for the treatment of virus-induced upper respiratory tract infections, peptic ulcers, viral pneumonia, etc. However, it has attracted widespread attention because it often causes adverse drug reactions (ADRs), including dyspnea. However, little is known about the mechanism underlying dyspnea caused by ZTOI, which limits its clinical application. AIM OF THE STUDY: To investigate the major pathophysiologic signatures and underlying mechanism of ZTOI-related dyspnea. METHODS: Respiratory function detection was used to explore the pathophysiologic signature of dyspnea induced by ZTOI. UV-vis absorption spectroscopy and isothermal titration calorimetry were applied to test the interaction between ZTOI and hemoglobin (Hb). GC‒MS was used to identify the main components in ZTOI. Molecular docking, surface plasmon resonance, and circular dichroism spectroscopy were employed to test the reaction between ß-elemene and Hb. Western blot was performed to investigate the effect of ß-elemene on the hypoxia signaling pathway. RESULTS: The results showed that ZTOI-induced dyspnea was related to a decreased oxygen carrying capacity of Hb. The molecular interaction between ZTOI and Hb was proven. Notably, ß-elemene in ZTOI exhibited high binding affinity to Hb and altered its secondary structure. Furthermore, it was found that ß-elemene downregulated the expression of prolyl hydroxylase-domain protein 2 and upregulated the expression of hypoxia-inducible factor-1α. CONCLUSIONS: Our study is valuable for better understanding the pathophysiological characteristics and underlying mechanism of ZTOI to ensure its safe clinical application. We also provided a strategy to elucidate the underlying mechanism based on inspiration from clinical ADR phenotypes for investigating other medical products with ADRs in the clinic.

Effect of Qigong exercise on motor function in stroke patients: a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Motor impairment is one of the most common defects after stroke, which could seriously affect the life quality of stroke patients. Exercise intervention gradually becomes a popular alternative rehabilitation therapy because of its safety and applicability. OBJECTIVES: To systematically assess the effect of Qigong exercise on motor function in stroke patients. METHODS: Randomized controlled trials that evaluated the effect of Qigong on motor function of stroke patients were obtained from PubMed and Chinese National Knowledge Infrastructure through May 2022. Mean values and standard deviations of the post-intervention score in both experimental group and control group were collected to calculate the mean difference (MD) and corresponkding 95% confidence interval (95% CI) of each study, which were quantificationally summarized using the Review Manager 5.3 software. RESULTS: Nineteen randomized controlled trials enrolling 1487 stroke patients were included. Pooled results indicated that Qigong exercise had beneficial effect on balance function (Berg Balance Scale [MD: 7.56, 95% CI: 4.09-11.02]), limb motor function (Fugl-Meyer Assessment [total score: MD: 7.54, 95% CI: 6.38-8.69; upper limb: MD: 3.57, 95% CI: 0.71-6.43; lower limb: MD: 2.44, 95% CI: 0.59-4.29]) and walking function (6-min walking test [MD: 62.21, 95% CI: 11.70-112.73]) of stroke patients. It was also found to be associated with an improvement in trunk function as indicated by the Trunk Impairment Scale. CONCLUSIONS: Available evidence supported potential benefits of Qigong exercise for improving motor functions of stroke patients. As a safe and widely applicable exercise, Qigong is worthy of further promotion in the rehabilitation of stroke patients.

Anti-obesity and Gut Microbiota Modulation Effect of Astragalus Polysaccharides Combined with Berberine on High-Fat Diet-Fed Obese Mice.

OBJECTIVE: To investigate whether astragalus polysaccharides (APS) combined with berberine (BBR) can reduce high-fat diet (HFD)-induced obesity in mice. METHODS: Except for normal mice, 32 HFD-induced obese mice were randomized into HFD, APS (1,000 mg/kg APS), BBR (200 mg/kg BBR), and APS plus BBR (1,000 mg/kg APS plus 200 mg/kg BBR) groups, respectively. After 6-week treatment (once daily by gavage), the obesity phenotype and pharmacodynamic effects were evaluated by histopathological examination of epididymal fat, liver, and colon using hematoxylin-eosin staining and serum biochemical analyses by an automated chemistry analyzer. The feces were collected at the 12 th week, and taxonomic and functional profiles of gut microbiota were analyzed by 16S ribosomal ribonucleic acid (16S rRNA) sequencing. RESULTS: Compared with HFD group, the average body weight of APS plus BBR group was decreased (P<0.01), accompanied with the reduced fat accumulation, enhanced colonic integrity, insulin sensitivity and glucose homeostasis (P<0.05 or P<0.01). Importantly, APS combined with BBR treatment was more effective than APS or BBR alone in improving HFD-induced insulin resistance (P<0.05 or P<0.01). 16S rRNA sequence-based analysis of fecal samples demonstrated that APS combined with BBR treatment exhibited a better impact on HFD-induced gut microbiota dysbiosis, exclusively via the enriched abundances of Bacteroides, which corresponded to the large increase of predicted bacterial genes involved in carbohydrate metabolism. CONCLUSION: APS combined with BBR may synergistically reduce obesity and modulate the gut microbiota in HFD-fed mice.

Progress in Mechanism of Astragalus membranaceus and Its Chemical Constituents on Multiple Sclerosis.

The primary chemical components of Astragalus membranaceus include polysaccharides, saponins, flavonoids, and amino acids. Recent studies have shown that Astragalus membranaceus has multiple functions, including improving immune function and exerting antioxidative, anti-radiation, anti-tumor, antibacterial, antiviral, and hormone-like effects. Astragalus membranaceus and its extracts are widely used in clinical practice because they have obvious therapeutic effects against various autoimmune diseases and relatively less adverse reaction. Multiple sclerosis (MS) is an autoimmune disease of central nervous system (CNS), which mainly caused by immune disorder that leads to inflammatory demyelination, inflammatory cell infiltration, and axonal degeneration in the CNS. In this review, the authors analyzed the clinical manifestations of MS and experimental autoimmune encephalomyelitis (EAE) and focused on the efficacy of Astragalus membranaceus and its chemical components in the treatment of MS/EAE.

Analysis of water quality indexes and their relationships with vegetation using self-organizing map and geographically and temporally weighted regression.

Natural vegetation has been proved to promote water purification in previous studies, while the relevant laws has not been excavated systematically. This research explored the relationships between vegetation cover and water quality indexes in Liaohe River Basin in China combined with self-organizing map (SOM) and geographically and temporally weighted regression (GTWR) innovatively and systematically based on the distributing heterogeneity of water quality conditions. Results showed that the central and northeast regions of the study area had serious organic and nutrient pollution, which needed targeted treatment. And SOM verified that high vegetation coverage with retention potential of organic and inorganic pollutants as well as nutrients improved water quality to some degree, while the excessive discharges of pollutants still had serious threats to nearby water environment despite the purification function of vegetation. GTWR indicated that the waterside vegetation was beneficial for dissolved oxygen increasing and contributed to the decreasing of organic pollutants and inorganic pollutants with reducibility. Natural vegetation also obsorbed nutrients like TN and TP to some degree. However, the retential potential of nitrogen and organic pollutants became not obvious when there were heavy pollution, which demonstrated that pollution sources should be controlled despite the purification function of vegetation. This study implied that natural vegetation purified water quality to some degree, while this function could not be revealed when there was too heavy pollution. These findings underscore that the pollutant discharge should be controlled though the natural vegetation in ecosystem promoted the purification of water bodies.

Progress in Mechanism of Astragalus membranaceus and Its Chemical Constituents on Multiple Sclerosis / 中国结合医学杂志

The primary chemical components of Astragalus membranaceus include polysaccharides, saponins, flavonoids, and amino acids. Recent studies have shown that Astragalus membranaceus has multiple functions, including improving immune function and exerting antioxidative, anti-radiation, anti-tumor, antibacterial, antiviral, and hormone-like effects. Astragalus membranaceus and its extracts are widely used in clinical practice because they have obvious therapeutic effects against various autoimmune diseases and relatively less adverse reaction. Multiple sclerosis (MS) is an autoimmune disease of central nervous system (CNS), which mainly caused by immune disorder that leads to inflammatory demyelination, inflammatory cell infiltration, and axonal degeneration in the CNS. In this review, the authors analyzed the clinical manifestations of MS and experimental autoimmune encephalomyelitis (EAE) and focused on the efficacy of Astragalus membranaceus and its chemical components in the treatment of MS/EAE.

Biomimetic Red Blood Cell Membrane-Mediated Nanodrugs Loading Ursolic Acid for Targeting NSCLC Therapy.

As one of the most common cancers worldwide, non-small-cell lung cancer (NSCLC) treatment always fails owing to the tumor microenvironment and resistance. UA, a traditional Chinese medicine, was reported to have antitumor potential in tumor models in vitro and in vivo, but showed impressive results in its potential application for poor water solubility. In this study, a novel biomimetic drug-delivery system based on UA-loaded nanoparticles (UaNPs) with a red blood cell membrane (RBCM) coating was developed. The RBCM-coated UANPs (UMNPs) exhibited improved water solubility, high stability, good biosafety, and efficient tumor accumulation. Importantly, the excellent antitumor efficiency of the UMNPs was confirmed both in vitro and in vivo in cancer models. In addition, we further investigated the antitumor mechanism of UMNPs. The results of Western blotting showed that UMNPs exerted an anticancer effect by inducing the apoptosis and autophagy of NSCLC cells, which makes it superior to free UA. In addition, body weight monitoring, hematoxylin and eosin (HE) analysis, and immunohistochemical (IHC) analysis showed no significant difference between UMNPs and the control group, indicating the safety of UMNPs. Altogether, the preparation of biomimetic UMNPs provides a promising strategy to improve outcomes in NSCLC.

[Rationality evaluation of Shuanghuanglian Injection combined with Ampicillin Sodium for Injection based on sequential analysis].

The lack of rationality evaluation method for drug combination has long restricted its clinical application. In view of this, this study took Shuanghuanglian Injection as model drug and established a "physical-chemical-biological" sequential analysis method, which is expected to provide clues for improving the safety and effectiveness of clinical drug combination. With the methods of insoluble particle testing, isothermal titration calorimetry(ITC), and real time cellular analysis(RTCA), the rationality of Shuanghuanglian Injection combined with Ampicillin Sodium for Injection was assessed. The results showed that the number of insoluble particles>10 µm in the solution of the combination met the standard of Chinese Pharmacopoeia, while the number of insoluble particles>25 µm did not meet the standard. ITC detection demonstrated that the change of Gibbs free energy(ΔG) was less than 0 during the fusion process, indicating that the process was spontaneous and enthalpy-driven reaction. Therefore, the interaction between the two was mainly chemical reaction, and the internal substances may change. RTCA found that Shuanghuanglian Injection alone and Ampicillin Sodium for Injection alone basically had no inhibitory effect on the growth of HEK293 T cells, while the combination of the two suppressed the growth of HEK293 T cells, suggesting that the combination was toxic to HEK293 T cells. This study showed that Shuanghuanglian Injection and Ampicillin Sodium for Injection reacted, yielding toxicity. This suggested that the two should not be combined for application. With the "physical-chemical-biological" sequential analysis, the molecular interaction of drugs was clarified. The method can be further applied for evaluating the rationality of other Chinese and western medicine injections.

Network pharmacology-based dissection of the underlying mechanisms of dyspnoea induced by zedoary turmeric oil.

Zedoary turmeric oil (ZTO) has been widely used in clinic. However, the unpleasant induced dyspnoea inevitably impedes its clinical application. Thus, it is urgent to elucidate the mechanism underlying the ZTO-induced dyspnoea. In this study, network pharmacology was firstly performed to search the clue of ZTO-induced dyspnoea. The key target genes of ZTO-induced dyspnoea were analysed using GO enrichment analysis and KEGG pathway analysis. GO analysis suggested that haem binding could be a key molecular function involved in ZTO-induced dyspnoea. Hence, the haemoglobin (Hb) was focused for its oxygen-carrying capacity with haem as its critical component binding to the oxygen. Ultraviolet-visible absorption spectrum indicated that the ZTO injection (ZTOI) perturbed the Soret band of Hb, suggesting an interaction between ZTO and Hb. GC-MS analysis revealed that ß-elemene, germacrone, curdione and furanodiene were main components of ZTOI. Molecular docking was used to illustrate the high affinity between representative sesquiterpenes and Hb, which was finally confirmed by surface plasmon resonance, suggesting their potential roles in dyspnoea by ZTO. Following a network pharmacology-driven strategy, our study revealed an intervened Hb-based mechanism underlying the ZTO-induced dyspnoea, providing a reference for elucidating mechanism underlying adverse drug reactions of herbal medicines in clinic.

Animal Model Analysis of Multiple Sclerosis Based on Clinical Characteristics of Traditional Chinese and Western Medicine / 中国实验方剂学杂志

Based on the clinical characteristics of multiple sclerosis （MS） in traditional Chinese medicine （TCM） and western medicine and literature analysis， this paper aims to formulate the diagnostic criteria of TCM and western medicine for MS. Moreover， the modeling methods of experimental autoimmune encephalomyelitis （EAE）， animals for the modeling， and characteristics of the models were analyzed and summarized， and the consistency between the EAE models and the diagnostic criteria of TCM and western medicine was evaluated. The results showed that animal models had low consistency with the clinical characteristics in TCM （highest consistency 68%） and western medicine （highest consistency 60%）. Pathological models account for the majority of animal models for MS research， but there is a lack of intuitive performance indicators. Thus， it is difficult to comprehensively evaluate the models. The mental state， limb numbness， lack of strength， loss of muscle tone， tremor， and balance disorders of the mice are among the diagnostic criteria in western medicine. In TCM diagnostic criteria， the major symptoms which are reflected in animal behavior， such as physical fatigue， lack of strength， mental fatigue， distinclination to talk， and weak heavy numb limbs， are consistent with the western diagnostic criteria. The minor symptoms， including mental decline， bitter taste in mouth， frequent and urgent urination， fecal incontinence， and aggravated fever， are not well reflected in the models. According to TCM， MS is caused by deficiency of kidney essence and external contraction of pathogen， but no index is available for evaluating the external contraction of pathogen in existing animal models. The key to experimental research on MS is to establish an appropriate animal model based on the clinical pathogenesis and characteristics. However， there is a lack of MS animal model with TCM characteristics for syndrome classification. Therefore， renewed efforts should be made to prepare animal models with both TCM and western medicine characteristics that can be used in both basic experiments and clinical research.

[Mechanism of Jinqi Jiangtang Tablets in treatment of pancreatic ß cell dysfunction based on network pharmacology and molecular docking technology].

The present study investigated the therapeutic efficacy and potential mechanism of Jinqi Jiangtang Tablets(JQJT) on pancreatic ß cell dysfunction based on network pharmacology and molecular docking technology. TCMSP platform was used to retrieve the chemical components and targets of the three Chinese herbal medicines of JQJT. The genes were converted to gene symbol by the UniProt, and its intersection with targets related to pancreatic ß cell function in GeneCards and CTD databases was obtained. The drugs, active components and common targets were imported into Cytoscape 3.8.2 to plot the drug-component-target network. The main effective components and targets were obtained by software analysis. The drug targets and targets related to pancreatic ß cell function were imported separately into the STRING platform for the construction of protein-protein interaction(PPI) networks. The two PPI networks were merged by Cytoscape 3.8.2 and the key targets were obtained by plug-in CytoNCA. The targets obtained from drug-component-target network and PPI networks were imported into DAVID for GO analysis and KEGG enrichment analysis. AutoDock was used to carry out molecular docking of main active components and core targets and Pymol was used to plot the molecular docking diagram. The results showed that there were 371 active components and 203 targets related to JQJT and 2 523 targets related to pancreatic ß cell damage, covering 136 common targets. The results revealed core targets(such as PTGS2, PTGS1, NOS2, ESR1 and RXRA) and effective key components(such as quercetin, kaempferol, luteolin, ß-carotene and ß-sitosterol). KEGG enrichment analysis indicated that apoptosis, inflammation, and other signaling pathways were mainly involved. Molecular docking results showed that the main active components could spontaneously bind to the targets. This study preliminarily revealed the mechanism of JQJT in improving pancreatic ß cell damage through multi-component, multi-target and multi-pathway, and provided a theoretical basis for JQJT in the treatment of pancreatic ß cell dysfunction.

[Effect of intestinal flora changes on pharmacokinetics of astragaloside â £].

The effect of intestinal flora changes on the pharmacokinetics of astragaloside Ⅳ in rats with type 2 diabetes mellitus was explored in this study. The rat model in preliminary experiment was established by high-sugar and high-fat diet combined with the intraperitoneal injection of low-dose streptozotocin(STZ). Rats were divided into model group, astragaloside Ⅳ group, berberine group and combination group(five rats in each group). After two weeks of gavage, the rats' feces was taken for 16 S rRNA sequencing of intestinal flora. Pharmacokinetic experiments were performed on astragaloside Ⅳ in the four groups one day after the preliminary experiment. Plasma samples were precipitated in methanol with ginsenoside Rb_1 as an internal standard, and the plasma concentrations of astragaloside Ⅳ at different time points were determined by UPLC-MS/MS. The chromatographic separation was performed on a Waters Acquity UPLC BEH-C_(18) column(2.1 mm×100 mm, 1.7 µm) via gradient elution. The mobile phase was acetonitrile(A) and 5 mmol·L~(-1) ammonium formate solution with 0.2% formic acid(B). The flow rate was 0.4 mL·min~(-1), the injection volume 5 µL and the column temperature 40 ℃. The mass spectrometry was carried out with electrospray ionization source(ESI) in multiple reaction monitoring and positive ion modes. The specificity, linearity range, accuracy, precision, stability and dilution effect of the method all met the requirements for the determination of astragaloside Ⅳ in plasma. Plasma concentration-time curves were plotted and relevant pharmacokinetic parameters were calculated by DAS 3.2.8. The results showed that the concentration of absorbed astragaloside Ⅳ increased within 0-3.95 h and began to decline since 3.95 h. After 36 h, the metabolism was complete. The area under the plasma concentration-time curve(AUC_(0-t)) and the peak concentration(C_(max)) of astragaloside Ⅳ were increased in the three administration groups compared with the model group, but without significant difference, which suggested that the pharmacokinetic characteristics of saponin components would not necessarily change after the drug-induced alteration of intestinal flora.

Protective Effect of 20(R)-Ginsenoside Rg3 Against Cisplatin-Induced Renal Toxicity via PI3K/AKT and NF-[Formula: see text]B Signaling Pathways Based on the Premise of Ensuring Anticancer Effect.

Although the protective effect of ginsenoside on cisplatin-induced renal injury has been extensively studied, whether ginsenoside interferes with the antitumor effect of cisplatin has not been confirmed. In this paper, we verified the main molecular mechanism of 20(R)-ginsenoside Rg3 (R-Rg3) antagonizing cisplatin-induced acute kidney injury (AKI) through the combination of in vivo and in vitro models. It is worth mentioning that the two cell models of HK-2 and HepG2 were used simultaneously for the first time to explore the effect of the activation site of tumor-associated protein p53 on apoptosis and tumor suppression. The results showed that a single injection of cisplatin (20 mg/kg) led to weight loss, the kidney index of the mice increased, and creatinine (CRE) and blood urea nitrogen (BUN) levels in mice sharply increased. Continuous administration of R-Rg3 at doses of 10 and 20 mg/kg for 10 days could significantly alleviate this symptom. Similarly, R-Rg3 treatment reduced oxidative stress damage caused by cisplatin. Moreover, R-Rg3 could observably reduce the apoptosis and inflammatory infiltration of renal tubular cells induced by cisplatin. We used western blotting analysis to demonstrate that R-Rg3 restored cisplatin-induced AKI might be related to PI3K/AKT and NF-[Formula: see text]B mediated apoptosis and inflammation pathways. In the meantime, we also verified that R-Rg3 could activate different sites of p53 to control renal cell apoptosis induced by cisplatin without affecting its antitumor effect.

Network Pharmacology-Based Dissection of the Active Ingredients and Protective Mechanism of the Salvia Miltiorrhiza and Panax Notoginseng Herb Pair against Insulin Resistance.

The Salvia miltiorrhiza and Panax notoginseng herb pair (DQ) has been widely utilized in traditional Chinese medicine for the longevity and for preventing and treating cardio-cerebrovascular diseases. Often associated with cardio-cerebrovascular diseases are comorbidities such as insulin resistance. However, the protective mechanisms of DQ against insulin resistance remain not well understood. Through network pharmacology analysis, a total of 94 candidate active compounds selected from DQ (61 from S. miltiorrhiza Bunge and 33 from P. notoginseng (Burk.) F. H. Chen) interacted with 52 corresponding insulin resistance-related targets, which mainly involved insulin resistance and the AMPK signaling pathway. Furthermore, the contribution index calculation results indicated 25 compounds as the principal components of this herb pair against insulin resistance. Among them, ginsenoside F2, protocatechuic acid, and salvianolic acid B were selected and validated to promote glucose consumption through activating AMPK phosphorylation and upregulating GLUT4 in insulin-resistant cell model (HepG2/IR) cells. These findings indicated that DQ has the potential for repositioning in the treatment of insulin resistance mainly through the AMPK signaling pathway.

[Exploration on rationality evaluation approach of drug combination medication based on sequential analysis and machine learning].

Drug combination is a common clinical phenomenon. However, the scientific implementation of drug combination is li-mited by the weak rational evaluation that reflects its clinical characteristics. In order to break through the limitations of existing evaluation tools, examining drug-to-drug and drug-to-target action characteristics is proposed from the physical, chemical and biological perspectives, combining clinical multicenter case resources, domestic and international drug interaction public facilities with the aim of discovering the common rules of drug combination. Machine learning technology is employed to build a system for evaluating and predicting the rationality of clinical drug combinations based on "drug characteristics-repository information-artificial intelligence" strategy, which will be debugged and validated in multi-center clinical practice, with a view to providing new ideas and technical references for the safety and efficacy of clinical drug use.

The p53/p21/p16 and PI3K/Akt signaling pathways are involved in the ameliorative effects of maltol on D-galactose-induced liver and kidney aging and injury.

Successive evidence has established that maltol, a flavor-enhancing agent, could provide resistance to oxidative stress-induced tissue injury in various animal models though its benefits for aging-induced liver and kidney injuries are still undetermined. In the present work, for demonstrating maltol's ameliorative effect and probable mechanism against aging-induced liver and kidney injuries, D-galactose (D-Gal)-induced animal in vivo and HEK293 cells in vitro models were established and results demonstrated that long-term D-Gal treatment increases the accumulation of advanced glycation end products (AGEs) in liver and kidney tissues, mitigates cell viability, and arrests the cycle. Interestingly, 4-weeks maltol treatment at 50 and 100 mg/kg activated aging-associated proteins including p53, p21, and p16 followed by inhibiting malondialdehyde (MDA)'s over-production and increasing the levels of antioxidant enzymes. Therefore, decreases in cytochrome P450 E1 (CYP2E1) and 4-hydroxydecene (4-HNE)'s immunofluorescence expression levels are confirmed. Furthermore, maltol improved oxidative stress injury by activating the phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) signaling pathway. In conclusion, the purpose of the present study was to estimate the mechanistic insights into maltol's role as an antioxidant in liver and kidney cell senescence and injury, which will reflect potential of therapeutic strategy for antiaging and aging-related disease treatment.

Potential Role of Gut Microbiota in Traditional Chinese Medicine against COVID-19.

The coronavirus disease 2019 (COVID-19) spreads and rages around the world and threatens human life. It is disappointing that there are no specific drugs until now. The combination of traditional Chinese medicine (TCM) and western medication seems to be the current more effective treatment strategy for COVID-19 patients in China. In this review, we mainly discussed the relationship between COVID-19 and gut microbiota (GM), as well as the possible impact of TCM combined with western medication on GM in the treatment of COVID-19 patients, aiming to provide references for the possible role of GM in TCM against COVID-19. The available data suggest that GM dysbiosis did occur in COVID-19 patients, and the intervention of GM could ameliorate the clinical condition of COVID-19 patients. In addition, TCMs (e.g., Jinhua Qinggan granule, Lianhua Qingwen capsule, Qingfei Paidu decoction, Shufeng Jiedu capsule, Qingjin Jianghuo decoction, Toujie Quwen granules, and MaxingShigan) have been proven to be safe and effective for the treatment of COVID-19 in Chinese clinic. Among them, Ephedra sinica, Glycyrrhiza uralensis, Bupleurum chinense, Lonicera japonica,Scutellaria baicalensi, and Astragalus membranaceus are common herbs and have a certain regulation on GM, immunity, and angiotensin converting enzyme 2 (ACE2). Notably, Qingfei Paidu decoction and MaxingShigan have been demonstrated to modulate GM. Finally, the hypothesis of GM-mediated TCM treatment of COVID-19 is proposed, and more clinical trials and basic experiments need to be initiated to confirm this hypothesis.

Target separation and antitumor metastasis activity of sesquiterpene-based lysine-specific demethylase 1 inhibitors from zedoary turmeric oil.

Lysine-specific histone demethylase 1 (LSD1) was the first histone demethylase identified in epigenetics and has recently emerged as an attractive therapeutic target for treating tumors. To date, almost all reported LSD1 inhibitors have been chemosynthesized; however, natural products possess pharmacological and biological activity and can be sources for drug development. Here, we established a target separation countercurrent chromatography technique to isolate LSD1 inhibitors from zedoary turmeric oil. Four sesquiterpene-based LSD1 inhibitors were efficiently obtained with an inhibition ratio equal to or less than that of the positive control drug. Compound 2 showed the most potent inhibitory activity, with a half-maximal inhibitory concentration of 3.97 µM, and was further tested to determine its ability to inhibit LSD1 and its antitumor metastatic effects in MDA-MB-231 cells. These four compounds are the first sesquiterpene-based natural LSD1 inhibitors to be characterized. Our findings provide a new molecular framework for studying LSD1 inhibitors and offer a template for designing more sesquiterpene-based LSD1 inhibitors with potential antitumor activity.