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A new phenolic compound oleiphenol (1), and a new dihydrochalcone oleifechalcone (2) along with seven known compounds (3-9) were isolated from the fruit shell of Camellia oleifera Abel. The planar structures of compounds 1 and 2 were determined on the basis of extensive spectroscopic analyses (IR, UV, NMR, and HR-ESI-MS) and comparison with literature data. The absolute configurations of the new structures were determined by ECD calculations and chemical methods. In addition, compounds 1-9 underwent a series of pharmacological activity tests, including cytotoxic, anti-inflammatory, anti-RSV and antioxidant activities. [ABSTRACT FROM AUTHOR]

Background: Determination of batch-to-batch consistency of botanical drugs (BDs) has long been the bottleneck in quality evaluation primarily due to the chemical diversity inherent in BDs. This diversity presents an obstacle to achieving comprehensive standardization for BDs. Basically, a single detection mode likely leads to substandard analysis results as different classes of structures always possess distinct physicochemical properties. Whereas representing a workaround for multi-target standardization using multi-modal data, data processing for information from diverse sources is of great importance for the accuracy of classification. Methods: In this research, multi-modal data of 78 batches of Guhong injections (GHIs) consisting of 52 normal and 26 abnormal samples were acquired by employing HPLC-UV, -ELSD, and quantitative 1H NMR (q1HNMR), of which data obtained was then individually used for Pearson correlation coefficient (PCC) calculation and partial least square-discriminant analysis (PLS-DA). Then, a mid-level data fusion method with data containing qualitative and quantitative information to establish a support vector machine (SVM) model for evaluating the batch-to-batch consistency of GHIs. Results: The resulting outcomes showed that datasets from one detection mode (e.g., data from UV detectors only) are inadequate for accurately assessing the product's quality. The mid-level data fusion strategy for the quality evaluation enabled the classification of normal and abnormal batches of GHIs at 100% accuracy. Conclusions: A quality assessment strategy was successfully developed by leveraging a mid-level data fusion method for the batch-to-batch consistency evaluation of GHIs. This study highlights the promising utility of data from different detection modes for the quality evaluation of BDs. It also reminds manufacturers and researchers about the advantages of involving data fusion to handle multi-modal data. Especially when done jointly, this strategy can significantly increase the accuracy of product classification and serve as a capable tool for studies of other BDs. [ABSTRACT FROM AUTHOR]

Diabetic kidney disease (DKD) is the primary cause of mortality among diabetic patients. With the increasing prevalence of diabetes, it has become a major concern around the world. The therapeutic effect of clinical use of drugs is far from expected, and therapy choices to slow the progression of DKD remain restricted. Therefore, research on new drugs and treatments for DKD has been a hot topic in the medical field. It has been found that rhein has the potential to target the pathogenesis of DKD and has a wide range of pharmacological effects on DKD, such as anti-nephritis, decreasing blood glucose, controlling blood lipids and renal protection. In recent years, the medical value of rhein in the treatment of diabetes, DKD and renal disease has gradually attracted worldwide attention, especially its potential in the treatment of DKD. Currently, DKD can only be treated with medications from a single symptom and are accompanied by adverse effects, while rhein improves DKD with a multi-pathway and multi-target approach. Therefore, this paper reviews the therapeutic effects of rhein on DKD, and proposes solutions to the limitations of rhein itself, in order to provide valuable references for the clinical application of rhein in DKD and the development of new drugs. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Nattokinase (NK) is a promising alternative in the prevention and treatment of cardiovascular diseases due to its potent fibrinolytic activity. In this study, we investigated the effect of crude nattokinase extract on the healing of acetic acid-induced oral mucositis in mice. Methods: Bacillus subtilis culture media (BSCM) was isolated into the supernatant, named nattokinase crude extract (NCE), and the pellet was named Bacillus subtilis mass (BSM). An oral mucositis model was established in mice by applying 50% glacial acetic acid to the buccal mucosa. According to the treatment conditions, the mice were divided into BSCM, NCE, BSM and phosphate buffered saline (PBS) groups. The weight of the mice, oral mucositis healing score and histopathological examination were used to evaluate the treatment. Results: Fibrinolytic activities of BSCM, NCE and BSM were approximately 8069, 10,800 and 80 U/ml, respectively. The weight gain of mice in the NCE group was significantly different from the PBS group after three days' treatment (p < 0.05). The oral mucositis score of NCE group was significantly higher than other groups (p < 0.05). The differences in histopathology scores between the NCE and other groups were statistically significant (p < 0.01). Conclusions: NCE could possess remarkable potential to reduce pain and promote oral mucositis healing with minimal safety concerns. In this study, we first report that NCE from the supernatant of Bacillus subtilis can promote the healing of oral mucositis, which extends the application scope of NK. [ABSTRACT FROM AUTHOR]

Objective. To systematically evaluate the efficacy and safety of XFZYD for coronary heart disease (CHD). Methods. A comprehensive literature search of randomized controlled trials using XFZYD for CHD was conducted in 10 electronic databases from their establishment to December 20, 2020. The researchers screened the relevant trials in NoteExpress, extracted the data in duplicate independently, assessed the risk of bias in the trials using the Cochrane collaboration tool, and then used Rev Man 5.3 for data analysis. Results. 30 trials with 3126 participants were included for meta-analysis. The results showed that the clinical effects of XFZYD and its combination with chemical drugs (CD) were 1.13 (RR; 1.13; 95% CI, 1.03 to 1.24) and 1.26 (RR; 1.26; 95% CI, 1.20 to 1.32) times those of CD, respectively. And, it could also improve electrocardiogram effect, which was 1.63 (RR; 1.63; 95% CI, 1.04 to 2.53) times that of CD. XFZYD could not only decrease duration of angina pectoris and improve vascular endothelial function but also obviously reduce the TCM syndrome score. When used in combination with CD, it could also lower AF, correct the dyslipidemia, and reduce the blood viscosity. Conclusion. These results demonstrated that XFZYD had great advantages in treating CHD with no obvious adverse reactions. Therefore, it is believed that XFZYD is more suitable for CHD patients with clinical indicators of dyslipidemia, high blood viscosity, or vascular endothelial dysfunction. This study is the first systematic review and meta-analysis with some unique ways, including its comprehensiveness, large-scale search, the novelty of findings, and transparent approach. [ABSTRACT FROM AUTHOR]

Thirteen undescribed dimeric Erythrina alkaloids, named as erythrivarines A1–A13, were isolated from the barks of Erythrina variegata L. and. Their structures were determined on the basis of NMR, UV and mass spectral analyses. Dimeric Erythrina alkaloid with a C-8/8′ linkage in erythrivarine A1 was not yet reported. Representative dimers from titled plant were used to prove their occurrence as natural products by LC − MS detection. Additionally, simultaneous investigation enabled us to propose the natural property of seemingly artificial Erythrina alkaloid with acetonyl group. Thirteen undescribed dimeric Erythrina alkaloids were isolated. Dimeric Erythrina alkaloid with a C-8/8′ linkage in erythrivarine A1 is not yet reported. Representative dimers from titled plant were proved their occurrence as natural products by LC-MS detection, which enabled us to propose the natural property of seemingly artificial products with acetonyl group. [Display omitted] [ABSTRACT FROM AUTHOR]

Tripterygium glycosides (TG) is extracted from the roots of Chinese herbal medicine named Tripterygium wilfordii Hook F (Tw HF). TG tablets are the representative Tw HF-based agents with anti-inflammatory and immunomodulatory activities for treating rheumatoid arthritis. Although the curative effect of TG is remarkable, the clinical application is limited by a variety of organ toxicity. One of the most serious side-effects induced by TG is damage of the male reproductive system and the toxic mechanism is still not fully elucidated. TG-induced testicular injury was observed in male mice by treated with different concentrations of TG. The results showed that TG induced a significant decrease in testicular index. Pathological observation showed that spermatogenic cells were obviously shed, arranged loosely, and the spermatogenic epithelium was thin compared with control mice. In addition, the toxic effect of TG on mouse spermatogonia GC-1 cells was investigated. The results displayed that TG induced significant cytotoxicity in mouse GC-1 cells. To explore the potential toxic components that triggered testicular injury, the effects of 8 main components of TG on the viability of GC-1 cells were detected. The results showed that celastrol was the most toxic component of TG to GC-1 cells. Western blot analysis showed that LC3-II and the ratio of LC3-II/LC3-I were significantly increased and the expression level of p62 were decreased in both TG and celastrol treated cells, which indicated the significant activation of autophagy in spermatogonia cells. Therefore, autophagy plays an important role in the testicular injury induced by TG, and inhibition of autophagy is expected to reduce the testicular toxicity of TG. • Tripterygium glycosides (TG) triggered significant testicular injury in mice. • Celastrol was the main toxic component of TG-induced toxicity to mouse spermatogonia GC-1 cell line. • TG and celastrol induced the autophagy of spermatogonia cells contributed to its testicular toxicity. [ABSTRACT FROM AUTHOR]

Based on the notion of traditional Chinese medicine, the theory of invigorating the circulation of blood is a prominent treatment for cancer in clinic. Therefore, Salvia miltiorrhiza Bunge, as a representative of Chinese medicine of invigorating the circulation of blood, has been proved to be an effective medicinal herb for treating cancer. To clarify the anti-cancer effect of Salvia miltiorrhiza Bunge aqueous extract (SMAE) on colorectal cancer (CRC) and investigate whether the therapeutic effect of SMAE was mediated by attenuating the infiltration of tumor-associated macrophages (TAMs) into the tumor microenvironment (TME). High-performance liquid chromatography (HPLC) was used for determined the main compounds of SMAE. MC38 cells were subcutaneously injected into the mice to establish the mouse model of CRC. Tumor growth curve was detected by tumor volume measurement. The model group received distilled water irrigation once a day. SMAE-treated group received 5 g/kg or 10 g/kg SMAE once a day. Anti-PD-L1 treated group received 5 mg/kg anti-PD-L1 once every three days. Protein expression of Cox2 and PD-L1 was determined by Western blot assay. The secretion levels of PGE2, IL-1β, IL-6, MCP-1, and GM-CSF were evaluated through ELISA. The mRNA expression of CSF1 , CCL2 , CXCL1 , CXCL2 , and CXCL3 was measured by using RT-qPCR. Staining of Ki67, TUNEL and Caspase3 was used to investigate cell proliferation and apoptosis. Immunohistochemical staining was used to determine CD8+ T cell distribution. H&E staining was used to confirm histopathological changes. The expressions of F4/80 and CD68 were measured by flow cytometry to identify macrophages in tumors and lymph nodes. The number of CD8+ T cells and the expression of PD-1, IFN-γ, and Granzyme B (GZMB) were determined by flow cytometry. SMAE significantly retarded the growth of MC38 mouse colorectal cancer. SMAE strikingly inhibited the expression of Cox2 and impaired the secretion of PGE2 in tumors, contributing to the attenuated intra-tumoral infiltration of TAMs via Cox2/PGE2 cascade. Meanwhile, SMAE augmented anti-tumor immunity by the elevated proportion of IFN-γ+ CD8+ T cells and GZMB+ CD8+ T cells, which decreased the tumor load. Furthermore, the combination of SMAE and anti-PD-L1 showed a higher therapeutic efficacy than either monotherapy in controlling tumor growth in MC38 xenograft model. SMAE attenuated the infiltration of TAMs into tumors and synergized with anti-PD-L1 to treat CRC via modulating Cox2/PGE2 cascade. SMAE inhibited the Cox2-mediated release of PGE2 and thus reshaped the tumor inflammatory microenvironment, resulting in the attenuated infiltration of TAMs while elevated the infiltration and killing function of CD8+ T cells. [Display omitted] • SMAE delayed tumor progression through modulating Cox2/PGE2 cascade in the mouse CRC model. • SMAE inhibited inflammation levels and hindered the infiltration of TAMs into the TME. • SMAE enhanced the infiltration and function of CD8+ T cells. • SMAE and PD-L1 blockade produced the synergistic anti-cancer impact in the mouse CRC model. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance : Sennoside A is a natural anthraquinone component mainly derived from rhubarb and has been routinely used as a clinical stimulant laxative. However, long-term application of sennoside A may lead to drug resistance and even adverse reactions, thus limiting its clinical use. Therefore, to reveal the time-dependent laxative effect and potential mechanism of sennoside A is of critical importance. Aim of the study : This study was conducted to investigate the time-dependent laxative effect of sennoside A and unveil its underlying mechanism from the perspective of gut microbiota and aquaporins (AQPs). Materials and methods : Based on a mouse constipation model, 2.6 mg/kg sennoside A was administered orally for 1, 3, 7, 14 and 21 days, respectively. The laxative effect was assessed by the fecal index and fecal water content, the histopathology of the small intestine and colon was evaluated by hematoxylin-eosin staining. Gut microbiota changes was observed by 16S rDNA sequencing, and colonic AQPs expression was analyzed by quantitative real-time polymerase chain reaction and western blotting. Partial least-squares regression (PLSR) was used to screen out the effective indicators contributing to the laxative effect of sennoside A. The effective indicators were then fitted to time by a drug-time curve model to analyze the trend of efficacy of sennoside A, and the optimal time of administration was derived by comprehensive analysis with a three-dimensional (3D) time-effect image. Results : Sennoside A had a significant laxative effect at 7 days of administration with no pathological changes in the small intestine or colon; however, at 14 or 21 days of administration, the laxative effect diminished and slight damage to the colon was observed. Sennoside A affects the structure and function of gut microbes. The alpha diversity showed that the abundance and diversity of gut microorganisms reached the highest value after 7 days of administration. Partial least squares discriminant analysis showed that the composition of the flora was close to normal when administered for less than 7 days, but was closest to the composition of constipation over 7 days. The expression of aquaporin 3 (AQP3) and aquaporin 7 (AQP7) decreased gradually after the administration of sennoside A, with the lowest expression at 7 days, and then increased gradually afterwards, while the expression of aquaporin 1 (AQP1) was the opposite. The PLSR results showed that AQP1, AQP3, Lactobacillus , Romboutsia , Akkermansia and UCG_005 contributed more to the laxative effect of the fecal index, and after fitting with the drug-time curve model, each index showed a trend of increasing and then decreasing. The comprehensive evaluation of the 3D time-effect image concluded that the laxative effect of sennoside A reached its best after 7 days of administration. Conclusion : Sennoside A should be used in regular dosages for less than one week, as it provides significant relief of constipation and exhibits no colonic damage within 7 days of administration. In addition, Sennoside A exerts its laxative effect by regulating gut microbiota of Lactobacillus Romboutsia , Akkermansia and UCG_005 and water channels of AQP1 and AQP3. [Display omitted] • For constipation relief, Sennoside A should be used at regular dose for less than 7 days. • Sennoside A exerts the laxative effect by regulating gut microbiota and aquaporins. • The optimal time is obtained through a comprehensive analysis of fecal index, intestinal histopathology, gut microbiota and aquaporins. [ABSTRACT FROM AUTHOR]