Metals/bisulfite system involved generation of 24-sulfonic-25-ene ginsenoside Rg1, a potential quality control marker for sulfur-fumigated ginseng.

Ginseng is a most popular health-promoting food with ginsenosides as its main bioactive ingredients. Illegal sulfur-fumigation causes ginsenosides convert to toxic sulfur-containing derivatives, and reduced the efficacy/safety of ginseng. 24-sulfo-25-ene ginsenoside Rg1 (25-ene SRg1), one of the sulfur-containing derivatives, is a potential quality control marker of fumigated ginseng, but with low accessibility owing to its unknown generation mechanism. In this study, metals/bisulfite system involved generation mechanism was investigated and verified. The generation of 25-ene SRg1 in sulfur-fumigated ginseng is that SO2, formed during sulfur-fumigation, reacted with water and ionized into HSO3-. On the one hand, under the metals/bisulfite system, HSO3- generates HSO5- and free radicals which converted ginsenoside Rg1 to 24,25-epoxide Rg1; on the other hand, as a nucleophilic group, HSO3- reacted with 24,25-epoxide Rg1 and further dehydrated to 25-ene SRg1. This study provided a technical support for the promotion of 25-ene SRg1 as the characteristic quality control marker of sulfur-fumigated ginseng.

The impacts of exogenous phosphorus on Cd absorption in perennial ryegrass root cell: Kinetic and mechanism study.

Phosphorus (P) is critical to plants in metal-contaminated soils because it participates in various biochemical reactions during plant growth. However, the mechanisms of P in mitigating the toxicity of heavy metals to ryegrass root is still veiled. In this study, the physiological and biochemical dynamics of the ryegrass root under various cadmium (Cd) and P conditions were investigated in a hydroponic system. Cd stress decreased the length of the ryegrass root, but P application enhanced the root elongation to reduce the Cd concentration in the root. Both Cd and P dosages were positively correlated with hemicellulose 1 content, pectin content, and PME activity, while having a negative effect on cellulose content. Moreover, the addition of 80 mg L-1 P increased the contents of pectin and hemicellulose 1 by 2.5 and 5.8% even with 4 mg L-1 Cd. In addition, P supply increased pectin methylesterbase activity under Cd stress, which further changed the extra-cytoplasmic structures and cell wall composition. Thus, exogenous P promoted the immobilization of Cd onto the cell wall and protected protoplast primarily through indirectly regulating the binding capacity of the root cell wall for Cd.

Evaluating the Significance of Titanium Clip Marking Under Endoscopy in Upper Gastrointestinal Bleeding Patients with Failed Endoscopic Hemostasis.

Objective: This study investigated the role of titanium clip marking during endoscopy in managing patients with upper gastrointestinal bleeding (UGIB) for whom endoscopic hemostasis has proven ineffective. Methods: A total of 63 UGIB patients admitted to the Affiliated Hospital of Zunyi Medical University between January 2018 and November 2020 were selected as the study cohort. Patients were randomly assigned to one of two groups: the control group (n=23) and the combined group (n=40). The control group underwent transcatheter arterial embolization (TAE), while the combined group received endoscopic metallic titanium clip-assisted TAE. This study compared the rates of successful embolization, clinical success, recurrence, operation time, radiation exposure time, radiation dosage, levels of hs-CRP, Cor, NE, TNF-α, IL-6, and ADH before and after treatment, as well as postoperative complications between the two groups. Results: The combined group of patients exhibited significantly higher rates of successful embolization and clinical success compared to the control group (P < .05). Additionally, the recurrence rate and levels of hs-CRP, Cor, NE, TNF-α, IL-6, and ADH were significantly lower in the combined group compared to the control group (P < .05). Furthermore, patients in the combined group had shorter operation times, reduced radiation exposure times, and lower radiation dosages compared to the control group (P < .05). There was no statistically significant difference in the occurrence of postoperative complications between the two groups (P > .05). Conclusions: Using titanium clip marking during endoscopy provides valuable guidance in managing patients with upper gastrointestinal bleeding who have not responded to endoscopic hemostasis. This finding is especially relevant in digital subtraction angiography (DSA) and transcatheter arterial embolization (TAE) treatments. It enhances the clinical efficacy and safety of the procedure.

A rs-fMRI study of functional connectivity changes between thalamus and postcentral gyrus in patients with neuropathic pain after brachial plexus avulsion.

BACKGROUND: The neuropathic pain (NPP) after brachial plexus avulsion (BPA) is common and difficult to cure, and thalamus and postcentral gyrus have been accepted to be the key nodes of mechanisms and pathways for pain. However, little attention has been paid on the thalamus-postcentral gyrus functional connectivity changes in NP patients after BPA. METHODS: Eighteen patients with NPP after BPA and twenty age and gender matched healthy controls were enrolled and underwent resting-state functional MRI (rs-fMRI) scans in this study. The Pearson's r-value of functional connection (bilateral thalamus and postcentral gyrus as regions of interest) was generated and examined using two sample t-test. The linear regression analysis was used to select possible related factors, and multiple linear regression of the possible predictors was used to identify the variables that significantly predicted Visual Analogue Score (VAS). RESULTS: The standardized Pearson r-values of the left thalamus-right thalamus, left thalamus-left postcentral gyrus, left thalamus-right postcentral gyrus, right thalamus-left postcentral gyrus and right thalamus-right postcentral gyrus in the control group were 0.759 ± 0.242, 0.358 ± 0.297, 0.383 ± 0.270, 0.317 ± 0.295 and 0.333 ± 0.304, respectively. And the corresponding standardized Pearson r-values in patients group were 0.510 ± 0.224,0.305 ± 0.212,0.281 ± 0.225,0.333 ± 0.193 and 0.333 ± 0.210, respectively. The functional connectivity strength of the left thalamus-right thalamus in control group was significantly higher than that in the patients group (P < 0.05). Linear regression analysis showed that the functional connectivity strength of the left thalamus-right thalamus was negatively correlated with the patients' VAS score (P < 0.05). CONCLUSIONS: NPP patients after BPA had a significant pain-related bilateral thalamus functional connection reorganization, with the purpose to limit the pain signal inputs within the unilateral cerebral hemisphere.

Comparing steamed and wine-stewed Rehmanniae Radix in terms of Yin-nourishing effects via metabolomics and microbiome analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Rehmanniae Radix Praeparata (RRP), the processed root of Rehmannia glutinosa, has been widely used to treat Yin deficiency syndrome in traditional Chinese medicine. RRP is available in two forms: processed by steaming with water (SRR) or processed by stewing with yellow rice wine (WRR). Previous work has documented chemical differences in the secondary metabolomes and glycomes of SRR and WRR. AIM OF THE STUDY: This study aimed to compare SRR and WRR in terms of Yin-nourishing effects via metabolomics and microbiome analysis. MATERIALS AND METHODS: ICR mice were orally administered with thyroxine for 14 d to induce Yin deficiency. Changes in biochemical indices and histopathology were detected. Serum metabolomics analysis and microbial 16S rRNA sequencing were performed to compare the therapeutic effects and mechanisms between SRR and WRR in treating thyroxine-induced Yin deficiency. RESULTS: Both SRR and WRR decreased serum T3, T4 and MDA levels, and increased SOD activity. SRR more effectively decreased serum Cr, and ameliorated kidney injury, while WRR showed better regulation on ratio of cAMP/cGMP and serum TSH, and relieved thyroid injury. Both SRR and WRR regulated tyrosine, glycerophospholipid, and linoleic acid metabolism and the citric acid cycle. Additionally, SRR regulated fatty acid metabolism, while WRR influenced alanine, aspartate and glutamate metabolism, and bile acid biosynthesis. SRR significantly enriched the genera Staphylococcus and Bifidobacterium in the gut microbiome, while WRR significantly enriched the genera Akkermansia, Bacteroides and Parabacteroides, and decreased the abundance of Lactobacillus. CONCLUSIONS: SRR displayed better protective effects on kidney, while WRR showed stronger effects on thyroid in thyroxine-induced Yin deficient mice. These differences might be due to different regulating effects of SRR and WRR on the metabolome and gut microbiota.

Dietary supplementation with probiotics increases growth performance, improves the intestinal mucosal barrier and activates the Wnt/ß-catenin pathway activity in chicks.

BACKGROUND: Probiotics comprise effective feed additives that can replace antibiotics in animal livestock production. However, mono-strain probiotics appear less effective because of their instability. Therefore, the present study aimed to investigate dietary supplementation with compound probiotics (CPP) on growth performance, diarrhea rate and intestinal mucosal barrier, as well as the possible molecular mechanism, in chicks. In total, 360 1-day-old chicks of the Hy-Line Brown Chicks were randomly divided into the control group (CON, basal diet), chlortetracycline group (500 mg kg-1 CTC) and compound probiotics group (1000 mg kg-1 CPP, consisting of Bacillus subtilis, Bacillus licheniformis, Enterococcus faecium and yeast). The experiment period was 56 days. RESULTS: The results showed that, in comparison with the CON group, CPP significantly increased the average daily feed intake and average daily gain of chicks and reduced diarrhea (P < 0.05). The probiotic group exhibited increased immune organ (i.e. spleen and thymus) mass and increased levels of serum immunoglobulin (Ig)A, IgM and IgG (P < 0.05) compared to the CTC group. In addition, the jejunal mass and morphology were improved in the probiotic group (P < 0.05). Moreover, CPP reinforced jejunal barrier function, as indicated by increased transepithelial electrical resistance, protein expression of occludin and claudin-1, and diamine oxidase levels in the jejunum (P < 0.05). Likewise, enhanced fluorescence signals of proliferating cell nuclear antigen-labeled mitotic cells and villin-labeled absorptive cells in the jejunum (P < 0.05) suggested that CPP promoted intestinal stem cells activity. Mechanistically, the Wnt/ß-catenin signaling pathway, including ß-catenin, TCF4, c-Myc, cyclin D1 and Lgr5, was amplified in the jejunum by CPP addition (P < 0.05). CONCLUSION: The present study demonstrated that dietary supplementation with CPP reinforced the jejunal epithelial integrity by activating Wnt/ß-catenin signaling and enhanced immune function in chicks. © 2023 Society of Chemical Industry.

Analysis of proanthocyanidins and flavonols in the seedpods of Chinese Antique Lotus: A rich source of antioxidants.

Antique Lotus (Nelumbo) is a perennial aquatic plant with unique historical significance and cultural value, whereas its potential economic value hasn't been fully explored. The present study showed that lotus seedpods had significantly higher antioxidant capacity than other parts by FRAP, ABTS, and ORAC assays and analyzed the proanthocyanidins and flavonols in the seedpods of Antique Lotus. Polyphenols contributed to great antioxidant activity and 51 polyphenols were identified by UPLC-TQ-MS analysis. In which, 27 compounds were identified from lotus seedpods for the first time, including 20 trimers, 5 dimers and 2 tetramers of proanthocyanidin. Total proanthocyanidins explained 70%-90% of the different antioxidant activities and the content of proanthocyanidin trimers showed the strongest correlations with the antioxidant activities. This study provided a fundamental reference for the research of polyphenols in lotus and found that Antique Lotus seedpod extracts have the promising prospects of additives used in feed and food processing.

Fuzheng Xiaoai Decoction 1 ameliorated cancer cachexia-induced muscle atrophy via Akt-mTOR pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Fuzheng Xiaoai Decoction 1 (FZXAD1) is a clinical experience prescription for the treatment of cancer patients at an advanced stage. FZXAD1 has been used for more than 10 years in the clinic and can effectively improve the deficiency syndrome of cancer patients. However, its mechanisms need further clarification. AIM OF THE STUDY: To check the effects of FZXAD1 in colon 26 (C26) cancer cachexia mice and try to clarify the mechanisms of FZXAD1 in ameliorating cancer cachexia symptoms. MATERIALS AND METHODS: An animal model of cancer cachexia was constructed with male BALB/c mice bearing C26 tumor cells. Food intake, body weight and tumor size were measured daily during the animal experiment. Tissue samples in different groups including tumor and gastrocnemius muscle, were dissected and weighed at the end of the assay. Serum biochemical indicators such as total protein (TP), glucose (GLU) and alkaline phosphatase (ALP) were also detected. Network pharmacology-based analysis predicted the possible targets and signaling pathways involved in the effects of FZXAD1 on cancer cachexia therapy. Western blotting assays of the gastrocnemius muscle tissues from C26 tumor-bearing mice were then used to confirm the predicted possible targets of FZXAD1. RESULTS: The results of animal experiments showed that FZXAD1 could ameliorate cancer cachexia by alleviating the muscle wasting as well as kidney atrophy and increasing the body weight of cancer cachexia mice. AKT1, MTOR, MAPK3, HIF1A and MAPK1 were predicted as the core targets of FZXAD1. Western blotting confirmed the prediction that FZXAD1 increased the expression levels of phosphorylated Akt and mTOR in the muscle tissues. In addition, FZXAD1 treatment obviously ameliorated the increased levels of HIF-1α and phosphorylated Erk1/2 in C26 tumor-bearing mice. CONCLUSION: FZXAD1 effectively ameliorated cancer cachexia in an animal model of mice, which is consistent with its efficacy in the treatment of cancer patients. The mechanisms of FZXAD1 might be mainly based on its alleviating effects on muscle atrophy by activating the Akt-mTOR pathway and thus helping to maintain body weight.

Meta-analysis of acupuncture-moxibustion treatment of overactive bladder in adults in the past decade / 针灸推拿医学（英文版）

Objective: To systematically assess the effectiveness and safety of using acupuncture-moxibustion therapy alone to treat adult overactive bladder (OAB) by taking oral Western medication solely as the control, and to provide evidence-based reference for acupuncture-moxibustion treatment of OAB. Methods: A systemic search was conducted through China National Knowledge Infrastructure (CNKI), Wanfang Academic Journal Full-text Database (Wanfang), Chongqing VIP Database (CQVIP), China Biology Medicine Disc (CBM), PubMed, Cochrane Library, and Excerpta Medica Database (EMBASE). RevMan 5.3 was used for meta-analysis. Statistical descriptions were made using standardized mean difference (SMD), confidence interval (CI), and risk ratio (RR). Results: Eight randomized controlled studies were finally recruited and were analyzed after being grouped according to intervention methods. Regarding urinary symptoms, compared with sole use of oral Western medication, acupuncture plus moxibustion can more effectively reduce 24 h urinary frequency [P=0.01, SMD=-0.57, 95％CI (-1.02, -0.12)], 24 h nocturia frequency [P=0.03, SMD=0.49, 95％CI (0.05, 0.94)], and OAB syndrome score (OABSS) [P<0.001, SMD=-3.67, 95％CI (-4.48, -2.86)]. Acupuncture combined with moxibustion and oral Western medication work equivalently in comparing 24 h urinary urgency frequency [P=0.38, SMD=-0.17, 95％CI (-0.57, 0.22)], 24 h urgent incontinence frequency [P=0.25, SMD=0.26, 95％CI (-0.18, 0.70)], and single voiding volume [P=0.22, SMD=1.15, 95％CI (-0.70, 3.00)]. There were no significant differences between acupuncture/electroacupuncture and oral medication in comparing 24 h urinary frequency [P=0.46, SMD=0.07, 95％CI (-0.12, 0.26)], 24 h urinary urgency frequency [P=0.18, SMD=0.70, 95％CI (-1.71, 0.32)], 24 h nocturia frequency [P=0.46, SMD=-0.71, 95％CI (-2.60, 1.17)], 24 h urgent incontinence frequency [P=0.08, SMD=-0.22, 95％CI (-0.48, 0.03)], single voiding volume [P=0.09, SMD=0.17, 95％CI (-0.02, 0.36)], or OABSS [P=0.96, SMD=-0.07, 95％CI (-2.65, 2.52)]. Compared with oral Western medication, moxibustion can more effectively reduce 24 h urinary frequency [P<0.001, SMD=-6.53, 95％CI (-7.65, -5.44)] and 24 h urinary urgency frequency [P<0.001, SMD=-1.6, 95％CI (-2.85, -0.36)]. In comparing the adverse reaction rate, acupuncture-moxibustion was associated with a lower rate compared with oral medication [P=0.002, RR=0.07, 95％CI (0.01, 0.37)], but the difference was statistically insignificant between acupuncture/electroacupuncture and oral medication [P=0.40, RR=0.57, 95％CI (0.16, 2.12)]. Conclusion: Acupuncture-moxibustion is equivalent to the sole use of oral Western medication in improving urinary symptoms in OAB patients and has a higher safety rating.

[Dual regulation of Qizhiweitong particles on gastric motility in the model rats with gastroparesis].

This paper was aimed to study the effects of Qizhiweitong particles (QZWT) on gastric motility in gastroparesis model rats, and to provide a theoretical and experimental basis for its clinical treatment. Rat gastroparesis model was established by bilateral injection of 6-hydroxydopamine into the substantia nigra in male Sprague-Dawley (SD) rats. The model rats received single gastric feeding of 1, 10, 30, 100, 200, 450, or 675 mg/kg QZWT or continuous administration of 675 mg/kg QZWT per day for 7 days. The gastric motility was measured by gastric emptying study and in vivo digital X-ray imaging system. The in vivo and ex vivo gastric longitudinal muscle contraction was recorded by PowerLab biological signal acquisition system. Gastric myoelectric signals were recorded by wireless implantable telemetry system. Protein expression levels of proinflammatory proteases in the myometrium were determined by Western blot. The results showed that the single administration of QZWT dose-dependently inhibited the contractile activity of isolated gastric strips from normal rats. The single administration of QZWT inhibited the in vivo contraction of gastric smooth muscle and gastric myoelectric signal in the control and model rats. The gastric emptying rate, in vivo and ex vivo gastric motility and gastric myoelectric signal in the model rats were significantly decreased compared with those in the control rats; While the continuous administration of QZWT markedly improved all the above indices of gastric motility function. The single administration of QZWT inhibited isolated gastric muscle strip contraction, and neither atropine nor nitric oxide synthase inhibitor pretreatments affected QZWT's inhibitory effects. The continuous administration of QZWT down-regulated the increased protein expression levels of nitric oxide synthase and cyclooxygenase 2 in the model group. These results suggest that, in clinical treatment, the single administration of QZWT may induce an analgesic effect by rapidly inhibiting gastric motility, while this effect is not related to acetylcholine or nitric oxide pathways. Long-term treatment with QZWT may ameliorate gastric motility through enhancing myoelectric activities, gastric smooth muscle contraction and gastric emptying, and this effect may partly be related to its anti-inflammatory effect.

Cucurbitacin B-induced G2/M cell cycle arrest of conjunctival melanoma cells mediated by GRP78-FOXM1-KIF20A pathway.

Conjunctival melanoma (CM) is a rare and fatal malignant eye tumor. In this study, we deciphered a novel anti-CM mechanism of a natural tetracyclic compound named as cucurbitacin B (CuB). We found that CuB remarkably inhibited the proliferation of CM cells including CM-AS16, CRMM1, CRMM2 and CM2005.1, without toxicity to normal cells. CuB can also induce CM cells G2/M cell cycle arrest. RNA-seq screening identified KIF20A, a key downstream effector of FOXM1 pathway, was abolished by CuB treatment. Further target identification by activity-based protein profiling chemoproteomic approach revealed that GRP78 is a potential target of CuB. Several lines of evidence demonstrated that CuB interacted with GRP78 and bound with a K d value of 0.11 µmol/L. Furthermore, ATPase activity evaluation showed that CuB suppressed GRP78 both in human recombinant GRP78 protein and cellular lysates. Knockdown of the GRP78 gene significantly induced the downregulation of FOXM1 and related pathway proteins including KIF20A, underlying an interesting therapeutic perspective. Finally, CuB significantly inhibited tumor progression in NCG mice without causing obvious side effects in vivo. Taken together, our current work proved that GRP78-FOXM1-KIF20A as a promising pathway for CM therapy, and the traditional medicine CuB as a candidate drug to hinder this pathway.

Co-existing polysaccharides affect the systemic exposure of major bioactive ingredients in Chang-Kang-Fang, a multi-herb prescription for treatment of irritable bowel syndrome.

ETHNOPHARMACOLOGICAL RELEVANCE: Chang-Kang-Fang (CKF) is a traditional Chinese herbal formula used for treatment of irritable bowel syndrome (IBS) in China. Decoction is the administration form of CKF in clinical practice. Previously, CKF has been confirmed with activities of releasing pain and reversing disorders of intestinal propulsion. And alkaloids, monoglycosides, chromones were found as the main bioactive components potentially contributing to the efficacy of CKF. Polysaccharide was also a major constituent in CKF. But if and how polysaccharides influence the systemic exposure of bioactive components in CKF is unknown. AIM OF THE STUDY: In this study, we aimed to demonstrate the contribution of the co-existed polysaccharides on the systemic exposure of the major bioactive components from CKF in normal and IBS model rats. MATERIALS AND METHODS: An UPLC-TQ-MS with multiple reaction monitoring (MRM) scan method was developed and validated for quantifying six major small molecular bioactive ingredients of CKF in the plasma samples, including magnoflorine (MAG), berberine (BBR), albiflorin (ALB), paeoniflorin (PAE), 5-O-methylvisamminol (5-OM) and prim-O-glucosylcimifugin (POG). The rats received CKF decoction (CKF) and CKF small molecule portion (knockout of polysaccharides, CKFSM), respectively. IBS model rats were induced by daily bondage and gavage of Sennae Folium decoction (derived from the leaf of Cassia angustifolia Vahl). The effects of the co-existing polysaccharides on the pharmacokinetic parameters of six small molecular bioactive components in normal and IBS model rats were systematically evaluated. The potential gut microbiota involved mechanisms of the effects was validated by broad-spectrum antibiotic (ABX) treatment. RESULTS: The selectivity, precision, accuracy, recovery and matrix effect of the established quantification method were all within acceptable limits of biological sample. In normal rats, the co-existing polysaccharides significantly reduced the AUC(0-t) of MAG and PAE compared with CKFSM group. The Cmax and AUC(0-t) of other four compound were not influenced by co-existing polysaccharides. However, in IBS model rats, compared with CKFSM group, the Cmax and AUC(0-t) of the six ingredients significantly increased in CKF group. For CKF + ABX group, the Cmax of six ingredients decreased significantly when compared with CKF group, and the AUC(0-t) of MAG, BBR, ALB, PAE also reduced with significant differences. CONCLUSIONS: A reliable and sensitive UPLC-TQ-MS method was successfully developed and validated for evaluating influence of co-existing polysaccharides on pharmacokinetic behavior of six major small molecules components in CKF. The co-existing polysaccharides enhanced the systemic exposure of six bioactive small molecules in CKF under IBS pathological state potentially via gut microbiota involvement.

Effects of sulfur-fumigated ginseng on the global quality of Si-Jun-Zi decoction, a traditional ginseng-containing multi-herb prescription, evaluated by metabolomics and glycomics strategies.

Si-Jun-Zi decoction (SJZD) with ginseng as the principal medicinal herb is a traditional Chinese Medicine multi-herb prescription that commonly employed to treat colorectal cancer etc. Previous studies showed that nearly half of the commercial ginseng was sulfur-fumigated, one of the postharvest processing methods that commonly causes sulfur-dioxide (SO2) residue and chemical composition transformation in medical herbs. In this study, the effect of sulfur-fumigated ginseng on global quality of SJZD was evaluated by UPLC-QTOF-MS/MS based metabolomics and multiple chromatographic techniques based glycomics strategies. For non-saccharides components, sulfur-fumigated ginseng led to the emergence of sulfur-containing derivatives and alteration of saponins and flavonoids in SJZD. For saccharide components, sulfur-fumigated ginseng decreased the total contents and molecular weights of polysaccharides, changed the monosaccharide composition of polysaccharides, and increased the contents of oligosaccharides and free monosaccharides of SJZD. The alterations of SJZD were aggravated with the sulfur-fumigated content of ginseng. Those phenomena might be attributed to 1) sulfur-fumigation caused the generation of sulfur-containing derivatives in ginseng, which further transferred to SJZD, and 2) sulfur-fumigation caused the residue of SO2 in ginseng, which reduced the pH value and further changed the dissolution of saponins and flavonoids and accelerated the degradation of the polysaccharides to oligosaccharides and/or monosaccharides in SJZD. Furthermore, although storage reduced the SO2 residue in sulfur-fumigated ginseng, it couldn't recover the alterations of chemical profiles in SJZD. In conclusion, sulfur-fumigated ginseng altered the global quality of SJZD, which promoted that extra attention must be paid during the application of herbal formulas that containing sulfur-fumigated herbs.

[Critical quality attribute characterization of big brand TCM: taste formulation optimization strategy and application of Xiaoer Ganmao Oral Liquid based on taste quality attribute].

The taste is the quality attribute for the development and production of traditional Chinese medicine(TCM). To improve the medication compliance of the big brand TCM, Xiaoer Ganmao Oral Liquid, a correlation model between the electronic tongue sensor signal value and human sensory evaluation score was established, and an optimization strategy of taste improvement for Xiaoer Ganmao Oral Liquid was developed with the key techniques of statistical experimental design. Based on the above model, the optimal formulation was determined as follows: aspartame content of 1-2 mg·mL~(-1), acesulfame-K content of 1.5-3 mg·mL~(-1), and steviol glycoside content of 1-2 mg·mL~(-1). Furthermore, the optimal formulation was verified by human sensory evaluation. Therefore, the taste of Xiaoer Ganmao Oral Liquid was improved. Taking Xiaoer Ganmao Oral Liquid as an example, the present study developed the taste formulation optimization method based on the correlation between the electronic tongue and human sensory evaluation, which is expected to provide an important reference to improve the taste of oral liquid of TCM.

Effects and contributory factors of sulfur-fumigation on the efficacy and safety of medicinal herbs evaluated by meta-analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Sulfur-fumigation undoubtedly alters the chemical and metabolic profiles, but controversially affects the efficacy and safety of medicinal herbs. AIM OF THE STUDY: To comprehensively evaluate the effects of sulfur-fumigation on the efficacy and safety of medicinal herbs using a meta-analysis approach and further investigate the potential contributory factors. MATERIALS AND METHODS: Literatures were retrieved on PubMed, Web of Science, Embase, China National Knowledge Infrastructure, Chinese VIP Information and Wanfang, and the outcomes involved activities and toxicities were extracted using standard data extraction forms. The effects of sulfur-fumigation on the efficacy and safety of medicinal herbs were evaluated by meta-analysis approaches. RESULTS: A total of sixteen studies were included in this study. Sulfur-fumigation reduced the efficacies of medicinal herbs with immune activity [thymus index (SMD = -1.81; P < 0.00001); spleen index (SMD = -1.11; P < 0.0001)], anti-oxidative activity [MDA (SMD = 2.60; P = 0.04); SOD (SMD = -2.21; P < 0.00001)], analgesic activity [heat tolerate time (SMD = -2.51; P = 0.001); writhing time (SMD = 0.36; P = 0.006)], anti-platelet aggregation activity (SMD = -1.84; P = 0.001), and anti-inflammatory activity [ear swelling degree (SMD = 0.47; P = 0.006)]. The reductions might be ascribed to sulfur-fumigation significantly reduced the contents of active ingredients in medicinal herbs, leading to dramatic decrease in the absorption of these ingredients and their metabolites in vivo. Furthermore, sulfur-fumigation induced the toxicities of medicinal herbs, mainly on hepatotoxicity, which might due to fumigation-induced residues of sulfur dioxide and heavy metal, and generations of sulfur-containing derivatives and toxic metabolites. Besides, administrated with sulfur-fumigated medicinal herbs with high sulfur ratio and/or higher dosage showed more significant toxicity. CONCLUSION: Sulfur-fumigation reduced the efficacy and safety of medicinal herbs, indicating sulfur-fumigation might not a feasible approach to process medicinal herbs. However, with obvious limitations, much more rigorous designed-trials are still needed to confirm the conclusion.

Gut Microbiota Mediates the Protective Effects of Traditional Chinese Medicine Formula Qiong-Yu-Gao against Cisplatin-Induced Acute Kidney Injury.

Our previous study found that Qiong-Yu-Gao (QYG), a traditional Chinese medicine formula derived from Rehmanniae Radix, Poria, and Ginseng Radix, has protective effects against cisplatin-induced acute kidney injury (AKI), but the underlying mechanisms remain unknown. In the present study, the potential role of gut microbiota in the nephroprotective effects of QYG was investigated. We found that QYG treatment significantly attenuated cisplatin-induced AKI and gut dysbiosis, altered the levels of bacterial metabolites, with short-chain fatty acids (SCFAs) such as acetic acid and butyric acid increasing and uremic toxins such as indoxyl sulfate and p-cresyl sulfate reducing, and suppressed histone deacetylase expression and activity. Spearman's correlation analysis found that QYG-enriched fecal bacterial genera Akkermansia, Faecalibaculum, Bifidobacterium, and Lachnospiraceae_NK4A136_group were correlated with the altered metabolites, and these metabolites were also correlated with the biomarkers of AKI, as well as the indicators of fibrosis and inflammation. The essential role of gut microbiota was further verified by both the diminished protective effects with antibiotics-induced gut microbiota depletion and the transferable renal protection with fecal microbiota transplantation. All these results suggested that gut microbiota mediates the nephroprotective effects of QYG against cisplatin-induced AKI, potentially via increasing the production of SCFAs, thus suppressing histone deacetylase expression and activity, and reducing the accumulation of uremic toxins, thereby alleviating fibrosis, inflammation, and apoptosis in renal tissue. IMPORTANCE Cisplatin-induced acute kidney injury is the main limiting factor restricting cisplatin's clinical application. Accumulating evidence indicated the important role of gut microbiota in pathogenesis of acute kidney injury. In the present study, we have demonstrated that gut microbiota mediates the protective effects of traditional Chinese medicine formula Qiong-Yu-Gao against cisplatin-induced acute kidney injury. The outputs of this study would provide scientific basis for future clinical applications of QYG as prebiotics to treat cisplatin-induced acute kidney injury, and gut microbiota may be a promising therapeutic target for chemotherapy-induced nephrotoxicity.

[Atractylenolide â improves acetaminophen-induced acute liver injury in mice by inhibiting MAPK/NF-κB signaling pathway].

This study explored the protective effect of atractylenolide Ⅰ(AO-Ⅰ) against acetaminophen(APAP)-induced acute liver injury(ALI) in mice and its underlying mechanism. C57 BL/6 J mice were randomly divided into a control group, an APAP group(500 mg·kg~(-1)), a low-dose combination group(500 mg·kg~(-1) APAP + 60 mg·kg~(-1) AO-Ⅰ), and a high-dose combination group(500 mg·kg~(-1) APAP + 120 mg·kg~(-1) AO-Ⅰ). ALI was induced by intraperitoneal injection of APAP(500 mg·kg~(-1)). AO-Ⅰ by intragastric administration was performed 2 hours before APAP treatment, and the control group received the same dose of solvent by intragastric administration or intraperitoneal injection. The protective effect of AO-Ⅰ against APAP-induced ALI was evaluated by detecting alanine aminotransferase(ALT) and aspartate aminotransferase(AST) levels in the plasma and H&E staining in liver tissues of mice. The malondialdehyde(MDA) and glutathione(GSH) content and catalase(CAT) activity in mouse liver tissues were detected to evaluate the effect of AO-Ⅰ on APAP-induced oxidative stress in the liver. The proteins in the liver p38 mitogen-activated protein kinase(p38 MAPK), c-jun N-terminal kinase(JNK), and nuclear factor kappa-B p65(NF-κB p65) signaling pathways were measured by Western blot, and the liver inflammatory cytokines interleukin-1ß(IL-1ß) and interleukin-6(IL-6) were detected by real-time PCR. Compared with the APAP group, the combination groups showed reduced APAP-induced ALT level and liver MDA content, potentiated liver CAT activity, and elevated GSH content. Mechanistically, AO-Ⅰ treatment significantly inhibited APAP-up-regulated MAPK phosphorylation and NF-κB p65, and significantly reduced the transcriptional activities of IL-1ß and IL-6, downstream targets of NF-κB p65. AO-Ⅰ can improve APAP-induced ALI and the underlying mechanism is related to the inhibition of the MAPK/NF-κB p65 signaling pathway in APAP-challenged mice.

Antimicrobial Lignin-Based Polyurethane/Ag Composite Foams for Improving Wound Healing.

Antimicrobial materials are an urgent need for modern wound care in the clinic. Although traditional polyurethane foams have proven to be clinically valuable for wound treatment, their petroleum-originated preparation and bioinert nature have restricted their efficacy in biomedical applications. Here, we propose a simple one-step foaming method to prepare lignin-based polyurethane foams (LPUFs) in which fully biobased polyether polyols partially replace traditional petroleum-based raw materials. The trace amount of phenolic hydroxyl groups (about 4 mmol) in liquefied lignin acts as a direct reducing agent and capping agent to silver ions (less than 0.3 mmol), in situ forming silver nanoparticles (Ag NPs) within the LPUF skeleton. This newly proposed lignin polyurethane/Ag composite foam (named as Ag NP-LPUF) shows improved mechanical, thermal, and antibacterial properties. It is worth mentioning that the Ag NP-LPUF exhibits more than 99% antibacterial rate against Escherichia coli within 1 h and Staphylococcus aureus within 4 h. Evaluations in mice indicate that the antimicrobial composite foams can effectively promote wound healing of full-thickness skin defects. As a proof of concept, this antibacterial and biodegradable foam exhibits significant potential for clinical translation in wound care dressings.