Genus Paeonia monoterpene glycosides: A systematic review on their pharmacological activities and molecular mechanisms.

BACKGROUND: Genus Paeonia, which is the main source of Traditional Chinese Medicine (TCM) Paeoniae Radix Rubra (Chishao in Chinese), Paeoniae Radix Alba (Baishao in Chinese) and Moutan Cortex (Mudanpi in Chinese), is rich in active pharmaceutical ingredient such as monoterpenoid glycosides (MPGs). MPGs from Paeonia have extensive pharmacological effects, but the pharmacological effects and molecular mechanisms of MPGs has not been comprehensively reviewed. PURPOSE: MPGs compounds are one of the main chemical components of the genus Paeonia, with a wide variety of compounds and strong pharmacological activities, and the structure of the mother nucleus-pinane skeleton is similar to that of a cage. The purpose of this review is to summarize the pharmacological activity and mechanism of action of MPGs from 2012 to 2023, providing reference direction for the development and utilization of Paeonia resources and preclinical research. METHODS: Keywords and phrases are widely used in database searches, such as PubMed, Web of Science, Google Scholar and X-Mol to search for citations related to the new compounds, extensive pharmacological research and molecular mechanisms of MPGs compounds of genus Paeonia. RESULTS: Modern research confirms that MPGs are the main compounds in Paeonia that exert pharmacological effects. MPGs with extensive pharmacological characteristics are mainly concentrated in two categories: paeoniflorin derivatives and albiflflorin derivatives among MPGs, which contains 32 compounds. Among them, 5 components including paeoniflorin, albiflorin, oxypaeoniflorin, 6'-O-galloylpaeoniflorin and paeoniflorigenone have been extensively studied, while the other 28 components have only been confirmed to have a certain degree of anti-inflammatory and anticomplementary effects. Studies of pharmacological effects are widely involved in nervous system, endocrine system, digestive system, immune system, etc., and some studies have identified clear mechanisms. MPGs exert pharmacological activity through multilateral mechanisms, including anti-inflammatory, antioxidant, inhibition of cell apoptosis, regulation of brain gut axis, regulation of gut microbiota and downregulation of mitochondrial apoptosis, etc. CONCLUSION: This systematic review delved into the pharmacological effects and related molecular mechanisms of MPGs. However, there are still some compounds in MPGs whose pharmacological effects and pharmacological mechanisms have not been clarified. In addition, extensive clinical randomized trials are needed to verify the efficacy and dosage of MPGs.

Guasha improves knee osteoarthritis by inhibiting chondrocyte apoptosis and regulating expression of autophagy-related genes and proteins in rats. / åˆ®ç—§å¯¹è†å ³èŠ‚éª¨å ³èŠ‚ç‚Žå¤§é¼ è½¯éª¨ç»†èƒžå‡‹äº¡åŠè‡ªå™¬çš„å½±å“.

OBJECTIVES: To observe the effect of Guasha on inflammation factors, apoptosis and autophagy in the cartilage tissue of knee joint in rats with knee osteoarthritis (KOA), so as to explore its mechanisms underlying improvement of KOA. METHODS: A total of 51 male SD rats were randomized into three groups：blank control, KOA model and Guasha (n= 17 in each group) . The rats in the blank control group received intra-articular injection of 0.9% NaCl solution in the right knee joint. The KOA model was established by intraarticular injection of glutamate sodium iodoacetic acid in the right knee joint. For rats of the Guasha group, Guasha (at a frequency of 1 time/s, and an applied pressure of 0.3-0.5 kgf) was applied to "Yanglingquan" (GB34) and "Xuehai"(SP10) areas of the right leg, once every other day, for 7 consecutive sessions. The circumference of the right knee was measured, The histopathological changes of right knee cartilage were observed after H.E. staining. The contents of inflammatory factors interleukin (IL)-1ß and tumor necrosis factor (TNF)-α in the right knee articular cartilage tissue were assayed using ELISA. The expression levels of autophagy-related key molecule Beclin-1 (homologous series of yeast Atg6), light chain protease complication 3 type II/I (LC3II/LC3 I), ubiquitin binding factor 62 (P62) and cysteine aspartate protease-3 (Caspase-3) mRNAs and proteins of the right knee articular cartilage tissue were measured using real-time fluorescent quantitative PCR and Western blot, separately. The apoptosis of chondrocytes was assayed using TUNEL staining, and the immunoactivity of LC3 determined using immunofluorescence staining. RESULTS: After modeling, the right knee circumfe-rence of the model and Guasha groups was significantly increased compared with the blank control group (P<0.01), and after the intervention, the knee circumference of the Guasha group was markedly decreased in comparison with that of the model group (P<0.05). Results of H.E. staining showed obvious degeneration and defects in the cartilage tissue, necrosis of a large number of chondrocytes, fibrous hyperplasia, accompanied by inflammatory cell infiltration, osteoclast increase, fibroplasia and bone trabecular destruction in the model group, which was relatively milder in the Guasha group. Compared with the blank control group, the expression of Beclin-1 and LC3 mRNAs and proteins, and LC immunofluorescence intensity in the right knee articular cartilage tissue were significantly down-regulated (P<0.01, P<0.001), whereas the expression of P62 and Caspase-3 mRNAs and proteins, the apoptosis rate, contents of IL-1ß and TNF-α in the right knee articular cartilage tissue considerably increased (P<0.01, P<0.001) in the model group. In contrast to the model group, the Guasha group had an apparent increase in the expression levels of Beclin-1 and LC3 mRNAs and proteins and LC immunofluorescence intensity in the right knee articular cartilage tissue (P<0.05), and a pronounced decrease in the expression of P62 and Caspase-3 mRNAs and proteins, the apoptosis rate, and contents of IL-1ß and TNF-α in the right knee articular cartilage tissue (P<0.05, P<0.01). CONCLUSIONS: Guasha stimulation of GB34 and SP10 can improve joint cartilage damage in KOA rats, which may be associated with its functions in inhibiting the excessive release of inflammatory factors and apoptosis, possibly by down-regulating the expression of P62 and Caspase-3 mRNAs and proteins and up-regulating the expression of Beclin-1 and LC3 mRNAs and proteins, and by promoting autophagy of chondrocytes.

Bioassay-guided discovery and identification of new potent α-glucosidase inhibitors from Morus alba L. and the interaction mechanism.

ETHNOPHARMACOLOGICAL RELEVANCE: Morus alba L. (mulberry) is a well-known medicinal species that has been used by herbalist doctors for the treatment of diabetes for a long history, and modern ethnopharmacological studies have demonstrated the ameliorating effects of different mulberry extracts toward diabetes-related symptoms and identified a number of α-glucosidase inhibitors as hypoglycemic ingredients. AIM OF THE STUDY: The present study aims to explore new potent α-glucosidase inhibitors from the root bark of M. alba (known as Sang-Bai-Pi in traditional medicine) based on an in vivo antidiabetic evaluation of its extract fractions and further characterize the preliminary mechanism of the new active constituents. MATERIALS AND METHODS: α-Glucosidase inhibitory assay and diabetic mice model were used to locate and evaluate the active fractions from the extract. Diverse separation techniques (e.g. Sephadex LH-20 column chromatograph (CC) and HPLC) and spectroscopic methods (e.g. MS, NMR and ECD) were employed to isolate and structurally characterize the obtained constituents, respectively. Fluorescence quenching, kinetics and molecular docking experiments were conducted to investigate the enzyme inhibitory mechanism of the active compounds. RESULTS: The 80% ethanol eluate from the macroporous resin CC exerted good antidiabetic effects in the tested mice. Fifty-two flavonoids including 22 new ones were then separated and identified, and most of them showed strong inhibition against α-glucosidase with their structure-activity relationship being also discussed. The four new most active ingredients were further characterized to be mixed type of α-glucosidase inhibitors, and their binding modes with the enzyme were also explored. CONCLUSIONS: Our current work has demonstrated that the root bark of M. alba is an extremely rich source of flavonoids as potent α-glucosidase inhibitors and potential antidiabetic agents, which makes it a promising candidate species to develop new natural remedies for the prevention and treatment of diabetes.

Unraveling the evolutionary dynamics of the TPS gene family in land plants.

Terpenes and terpenoids are key natural compounds for plant defense, development, and composition of plant oil. The synthesis and accumulation of a myriad of volatile terpenoid compounds in these plants may dramatically alter the quality and flavor of the oils, which provide great commercial utilization value for oil-producing plants. Terpene synthases (TPSs) are important enzymes responsible for terpenic diversity. Investigating the differentiation of the TPS gene family could provide valuable theoretical support for the genetic improvement of oil-producing plants. While the origin and function of TPS genes have been extensively studied, the exact origin of the initial gene fusion event - it occurred in plants or microbes - remains uncertain. Furthermore, a comprehensive exploration of the TPS gene differentiation is still pending. Here, phylogenetic analysis revealed that the fusion of the TPS gene likely occurred in the ancestor of land plants, following the acquisition of individual C- and N- terminal domains. Potential mutual transfer of TPS genes was observed among microbes and plants. Gene synteny analysis disclosed a differential divergence pattern between TPS-c and TPS-e/f subfamilies involved in primary metabolism and those (TPS-a/b/d/g/h subfamilies) crucial for secondary metabolites. Biosynthetic gene clusters (BGCs) analysis suggested a correlation between lineage divergence and potential natural selection in structuring terpene diversities. This study provides fresh perspectives on the origin and evolution of the TPS gene family.

[Effect of moxibustion and scraping on bioactive substances changes of acupoints in knee osteoarthritis rats].

OBJECTIVE: To compare the effects of moxibustion and scraping of "Yanglingquan" (GB34) and "Xuehai" (SP10) area on changes of bioactive substances in the region of acupoints in rats with knee osteoarthritis (KOA). METHODS: SD rats were randomly divided into blank, model, moxibustion, scraping, and moxibustion + scraping (combination) groups, with 8 rats in each group. The KOA model was established by injecting 50 µL 0.9% sodium chloride solution into the right knee cavity. Fourteen days after modeling, GB34 and SP10 on the right limb were stimulated by moxibustion (10 min) or scraping (till regional flush) once every other day for 7 times. The mechanical paw withdrawal threshold (PWT) and thermal withdrawal latency (TWL) were tested by Von Frey and hot stabbing instrument, separately. The pathological changes of the right knee joint were observed by HE staining. The serotonin (5-HT) contents of skin tissues in the region of acupoint GB34 and SP10 were detected by ELISA. The expression levels of substance P (SP) and calcitonin gene-related peptide (CGRP) in GB34 and SP10 region skin tissues were detected by Western blot. RESULTS: Compared with the blank group, the PWT and TWL of the rats in the model group were significantly decreased (P<0.001), while the contents of 5-HT and the expression levels of SP and CGRP in GB34 and SP10 region skin tissues were significantly increased (P<0.001, P<0.01). Following intervention and in comparison the with the model group, the TWL and PWT of rats in the three treatment groups were significantly increased (P<0.01), the content of 5-HT and the expression levels of SP and CGRP in GB34 and SP10 region skin tissues were significantly decreased (P<0.01, P<0.001, P<0.05). Except for the expression levels of CGRP, the above indexes of the combination group were significantly superior to those of the moxibustion and scraping groups (P<0.05, P<0.01). Findings of HE staining showed severe damaged cartilage, few chondrocytes on the surface, with subchondral neovascularization in the model group, which was relatively milder in the moxibustion, scraping, and combination groups. CONCLUSION: Moxibustion and scraping can relieve knee joint pain in KOA rats, which may be associated with its function in down-regulating the expression levels of SP and CGRP, and the content of 5-HT. The therapeutic effect of moxibustion plus scraping is better than that of moxibustion and scraping alone.

Effect of cognitive training on patients with breast cancer reporting cognitive changes: a systematic review and meta-analysis.

OBJECTIVES: Cognitive training is a non-drug intervention to improve the cognitive function of participants by training them in different cognitive domains. We investigated the effectiveness of cognitive training for patients with breast cancer reporting cognitive changes. DESIGN: Systematic review and meta-analysis. DATA SOURCES: PubMed, Embase, Cochrane Library, WOS, CINAHL, CNKI, VIP, SinoMed, Wanfang, Grey literature and trial registries were searched (from inception to 1 October 1, 2022). ELIGIBILITY CRITERIA: Inclusion of randomized controlled trials (RCTs) assessing the effects of cognitive training on breast cancer patients reporting cognitive changes The primary outcome was subjective cognitive function. Secondary outcomes were objective cognitive functioning (eg, executive functioning and attention) and psychological outcomes(eg, anxiety, depression, and fatigue). DATA EXTRACTION AND SYNTHESIS: Two reviewers worked independently to screen the literature, extract data, and assess the methodological quality and risk bias of the included studies. Results are reported as standardizedstandardised mean differences (SMDs) with 95% confidence intervals(CI). Grades of Recommendation, Assessment, Development, and Evaluation(GRADE) were used to assess the quality of evidence. MAIN OUTCOMES AND MEASURES: The primary outcome was subjective cognitive function. Secondary outcomes were objective cognitive functioning (eg, executive functioning and attention) and psychological outcomes(eg, anxiety, depression and fatigue). RESULTS: A total of 9 RCTs involving 666 patients with breast cancer were included. The frequency of cognitive training varied and the duration was mostly focused on 5-12 weeks. It can be delivered to patients in an individual or group mode, both online and face to face. Meta-analysis revealed that cognitive training aimed at adaptive training in cognitive field has statistically significant effects on improving subjective cognitive function (SMD=0.30, 95% CI (0.08 to 0.51), moderate certainty). Some objective cognitive functions such as processing speed (SMD=0.28, 95% CI (0.02 to 0.54), low certainty), verbal memory (SMD=0.32, 95% CI (0.05 to 0.58), moderate certainty), working memory (SMD=0.39, 95% CI (0.17 to 0.61), moderate certainty) and episodic memory (SMD=0.40, 95% CI (0.11 to 0.69), moderate certainty) were significantly improved after the intervention. In addition, we did not find statistically significant changes in attention, short-term memory, execution function, depression, anxiety and fatigue in patients with breast cancer after the intervention. Subgroup analyses revealed that based on the delivery of individual sessions, the use of web-based cognitive training software may be more beneficial in improving the outcome of the intervention. CONCLUSION: Evidence of low to moderate certainty suggests that cognitive training may improve subjective cognition, processing speed, verbal memory, working memory and episodic memory in patients with breast cancer reporting cognitive changes. But it did not improve patients' attention, short-term memory, executive function, depression, anxiety and fatigue. PROSPERO REGISTRATION NUMBER: CRD42021264316.

Systematic elucidation of the bioactive alkaloids and potential mechanism from Sophora flavescens for the treatment of eczema via network pharmacology.

ETHNOPHARMACOLOGY RELEVANCE: Sophora flavescens is a frequently used traditional Chinese medicine (TCM) for the treatment of skin disorders, diarrhea, vaginal itching and inflammatory diseases. In particular, the root of S. flavescens combination with other herbs mainly treat eczema ailment in the clinical applications. However, a holistic network pharmacology approach to understanding the mechanism by which alkaloids in S. flavescens treat eczema has not been pursued. AIM OF THE STUDY: To examine the network pharmacological potential effect of S. flavescens on eczema, we studied the alkaloids, performed protein targets prediction and investigated interacting signal pathways. Furthermore, animal experiment was carried out to evaluate its efficacy and real-time quantitative polymerase chain reactions (RT-qPCR) analysis was explored the mechanism of action. MATERIALS AND METHODS: The detail information on alkaloids from S. flavescens were obtained from a handful of public databases on the basis of oral bioavailability (OB ≥ 30%) and drug-likeness (DL ≥ 0.18). Then, correlations between compounds and protein targets were linked using the STRING database, and targets associated with eczema were gathered by the GeneCards database. Human genes were identified and subjected to Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and Gene Ontology (GO) functional enrichment analysis. Particularly, matrine, the crucial alkaloid from S. flavescens, was estimated using a 2,4-dinitrochlorobenzene (DNCB)-induced eczema Kunming (KM) mice model, administered (50 mg/kg and 10 mg/kg) to mice for 22 days. On the last day, the activities of serum tumor necrosis factor α (TNF-α), interleukin-4 (IL-4) and histopathologic examinations were determined. For further to elucidate the mechanisms, the mRNA levels of TNF-α, STAT3, TP53, AKT1, IL-6, JUN and EGFR in dorsal skin tissues were also tested. RESULTS: Network analysis collected and identified 35 alkaloids from S. flavescens. Among them, in total 10 dominating alkaloids, including matrine, oxymatrine, sophoridine, sophocarpine, oxysophocarpine, allomatrine, sophoramine, anagyrine, cytisine and N-methylcytisine. And 71 related targets were provided of alkaloids for the treatment of eczema from S. flavescens. Furthermore, matrine dose-dependently (50 or 10 mg/kg, 22 days, apply to dorsal skin) remarkable decreased the serum levels of TNF-α and IL-4, and significantly alleviated the skin lesions. The effects of 50 mg/kg of matrine were almost identical to those of 200 mg/kg of the positive drug dexamethasone (DXM). The further RT-qPCR analyses could reveal that matrine down-regulate TNF-α, STAT3 and TP53 at transcriptional level in dorsal skin tissues. CONCLUSION: Pharmacological network analysis can utilize to illuminate the pharmacodynamic substances and the potential molecular mechanism of S. flavescens for treating eczema. Matrine, as the crucial alkaloid from S. flavescens, could be a promising drug candidate for the treatment of eczema ailment.

Ent-Abietane Diterpenoids from Euphorbia fischeriana and Their Cytotoxic Activities.

The roots of Euphorbia fischeriana have been used as a traditional Chinese medicine for the treatment of tuberculosis and ringworm. In the current study, diterpenoids from the ethyl acetate extract of the roots E. fischeriana and their cytotoxic effects against five cancer lines were investigated. Two new ent-abietane diterpenoids, euphonoids H and I (1-2), as well as their two analogues (3-4) were first isolated from this source. The structures of the two new compounds were elucidated on the basis of spectroscopic data and quantum chemical calculation. Their absolute configurations were assigned via ECD spectrum calculation. The isolated compounds were evaluated for their antiproliferative activities against five cancer cell lines. Compounds 1 and 2 exhibited significant inhibitory effects against human prostate cancers C4-2B and C4-2B/ENZR cell lines with IC50 values ranging from 4.16 ± 0.42 to 5.74 ± 0.45 µM.

[Distribution Characteristics of Soil Phosphorus Forms and Phosphatase Activity at Different Altitudes in the Soil of Water-Level-Fluctuation Zone in Pengxi River, Three Gorges Reservoir].

Phosphatases play important roles in converting organic phosphorus into inorganic phosphorus in soil. However, studies from this perspective on the water-level-fluctuation zone (WLFZ) of the Three Gorges Reservoir are limited. In this study, phosphatase activity and the forms of phosphorus were analyzed. Soil samples were collected in the river basin of the Penxi River in the WLFZ during a drying period. The correlation between phosphatase activity and phosphorus forms and the impacts of phosphatase activity on the phosphorus forms were analyzed. The results showed that the contents of H2O-Pi, NaHCO3-Pi, and NaOH-Pi in the soils of the WLFZ were higher than those in the soils by the river. In addition, a higher altitude resulted in higher contents of bio-enzymatically hydrolysable phosphorus and NaOH-Po. Furthermore, redundancy analysis (RDA) showed that the contents of organic matter and amorphous Fe and Mn were the main factors affecting soil organic phosphorus forms. The average activities of acid phosphomonoesterase (ACP), alkaline phosphomonoesterase (ALP), phosphodiesterase (PDE) (all in p-NP), and phytase (PAE) (in P) in the soils of the WLFZ were 1.40, 2.60, 0.44, and 11.43 µmol·(g·h)-1, respectively. Moreover, the activities of different phosphatases increased with altitude. Soil plant biomass and microbial biomass were important reasons for the difference in spatial distribution of phosphatase activity in the soil of the WLFZ. Phosphatase activities were significantly positively correlated with the contents of organic phosphorus forms but negatively correlated with the content of bioavailable phosphorus. A higher soil phosphatase activity and a lower content of bioavailable phosphorus were usually detected in soil samples taken at a higher altitude. In the early stage of flooding, phosphatase converted organic phosphorus into inorganic phosphorus at a relatively high rate, and the risk of phosphorus release to the overlying water body was also high. This study contributed to a comprehensive understanding of the geochemical cycle of soil phosphorus in the soil of the WLFZ.

Polygonum capitatum, the Hmong Medicinal Flora: A Comprehensive Review of Its Phytochemical, Pharmacological and Pharmacokinetic Characteristics.

Polygonum capitatum, known as "Tou Hua Liao" (Chinese name), is a crucial source of Hmong medicinal plants that has benefited human health for a long time. This folk-medicinal plant is widely distributed in the south-west of China for the treatment of various urologic disorders including urinary tract infections, pyelonephritis, and urinary calculus. The purpose of this paper was to provide a systematic and comprehensive overview of the traditional usages, botany, phytochemistry, pharmacology, pharmacokinetics and clinical applications of this flora. Up until the end of 2022, at least 91 compounds had been reported from P. capitatum, mainly covering the classes of flavonoids, lignanoids, phenols and other components. The compounds and extracts isolated from P. capitatum exhibit a wide range of pharmacological activities, such as anti-inflammatory, antioxidant, antimicrobial, anticancer, analgesic, hypothermic, diuretic and other pharmacological effects. Qualitative and quantitative chemical analyses were also covered. Furthermore, the possible development trends and perspectives for future research on this medicinal plant were also discussed.

Deciphering the Molecular Mechanisms of Chilling Tolerance in Lsi1-Overexpressing Rice.

Improving tolerance to low-temperature stress during the rice seedling stage is of great significance in agricultural science. In this study, using the low silicon gene 1 (Lsi1)-overexpressing (Dular-OE) and wild-type rice (Dular-WT), we showed that Lsi1 overexpression enhances chilling tolerance in Dular-OE. The overexpression of the Lsi1 increases silicon absorption, but it was not the main reason for chilling tolerance in Dular-OE. Instead, our data suggest that the overexpression of a Lsi1-encoding NIP and its interaction with key proteins lead to chilling tolerance in Dular-OE. Additionally, we show that the high-mobility group protein (HMG1) binds to the promoter of Lsi1, positively regulating its expression. Moreover, Nod26-like major intrinsic protein (NIP)'s interaction with α and ß subunits of ATP synthase and the 14-3-3f protein was validated by co-immunoprecipitation (Co-IP), bimolecular fluorescent complementary (BiFC), and GST-pulldown assays. Western blotting revealed that the overexpression of NIP positively regulates the ATP-synthase subunits that subsequently upregulate calcineurin B-like interacting protein kinases (CIPK) negatively regulating 14-3-3f. Overall, these NIP-mediated changes trigger corresponding pathways in an orderly manner, enhancing chilling tolerance in Dular-OE.

An unusual indole-diterpenoid with C-17 norcassane skeleton from Euphorbia fischeriana induces HEL cell cycle arrest and apoptosis.

Two new polycyclic diterpenoids, euphkanoids H and I (1 and 2), along with 6 known analogues (2-8) were isolated from the roots of Euphorbia fischeriana, a traditional Chinese medicine. Their structures were identified by spectral methods, and the absolute configurations of 1 and 2 were determined by ECD calculation and single crystal X-ray diffraction, respectively. Compound 1 represents the first example of C-17 norcassane indole-diterpenes. All the isolates were screened for antiproliferative activity against a panel of human cancer cell lines using the MTT assay, and 1 showed significant cytotoxicity against HEL cells (IC50 = 3.2 µM). Simple mechanistic study revealed that 1 could induce cell cycle arrest at G0/G1 phase and apoptosis in HEL cells.

Traditional Chinese Medicine Shen-Yuan-Dan (SYD) Improves Hypoxia-Induced Cardiomyocyte Apoptosis in Neonatal Rats by Upregulating miR-24/Bim Pathway.

Background: Acute myocardial infarction (AMI) is the leading cause of malignant arrhythmia, heart failure, and sudden death. However, safe and effective drugs for the treatment of AMI are unavailable to date. The present study aimed to investigate the role of traditional Chinese medicine shen-yuan-dan (SYD) in hypoxia-induced cardiomyocyte apoptosis in neonatal rats. In addition, the study explored the possible mechanism through which SYD could reduce myocardial ischemia apoptosis and regulate the expression of the miR-24/Bim pathway. Methods: Hypoxia-induced neonatal rat cardiomyocytes were used for the experiments. These cardiomyocytes were transfected with an miR-24 mimic and an miR-24 inhibitor and then cocultured with SYD-containing serum. MTT and lactate dehydrogenase (LDH) assays, AnnexinV/PI double staining, flow cytometry, and TUNEL staining were used to determine the cell viability and apoptosis under hypoxic conditions. Furthermore, the expression level of Bim in the hypoxia-induced cardiomyocytes was determined through western blotting and quantitative real-time polymerase chain reaction. Results: After 48 h of hypoxia, LDH and creatine phosphokinase (CPK) activities increased, cell viability decreased, and miR-24 expression upregulated in the cardiomyocytes. SYD alleviated hypoxia-induced cardiomyocyte injury, decreased LDH and CPK activities, increased cell viability, and reduced apoptosis in the neonatal rat cardiomyocytes. Moreover, SYD could upregulate miR-24 expression and downregulate Bim expression. Upregulation of miR-24 expression significantly enhanced the effect of SYD, thereby improving myocardial cell apoptosis. Dual-luciferase reporter assay and western blot analysis confirmed that Bim was a direct target of miR-24. Conclusion: SYD treatment reduces hypoxia-induced myocardial apoptosis by upregulating miR-24 expression. This study provides new insights into the molecular mechanism underlying the therapeutic potential of SYD in promoting the recovery of myocardial function and delaying the incidence of heart failure.

Mechanism of Baihe Dihuangtang in Treatment of Depression with Yin Deficiency and Internal Heat / 中国实验方剂学杂志

ObjectiveTo establish a traditional Chinese medicine （TCM） syndrome model with yin deficiency and internal heat， discuss the rationality of model evaluation， and analyze differentially expressed genes in multiple dimensions to explore the molecular mechanism-signaling pathways as well as key targets of Baihe Dihuangtang （BHDH） in treating depression with Yin deficiency and internal heat. MethodForty male SD rats were randomly divided into a blank control group，a model group，a fluoxetine group （positive drug），a BHDH group， and a Zhibai Dihuangtang group （positive drug for Yin deficiency and internal heat）. The depression model with Yin deficiency and internal heat was induced by chronic unpredictable mild stress （CUMS）combined with Chinese herbal drugs with warm and heat nature. The model established was comprehensively evaluated by the detection of the basic condition， behavioral performance， and biochemical indicators of rats in each group. The differentially expressed genes were screened out by mRNA sequencing and underwent Gene Ontology（GO） and Kyoto Encyclopedia of Genes and Genomes（KEGG） pathway enrichment analyses. The protein-protein interaction （PPI） network was plotted and key genes were analyzed to explore the underlying mechanism of BHDH in treating depression with Yin deficiency and internal heat. ResultThe comparison of basic conditions， behavioral assays， energy metabolism， endocrine hormones， cytokines， and neurotransmitters showed that the model was properly induced. BHDH could significantly improve depression with Yin deficiency and internal heat by regulating the pathways related to the nervous system， endocrine system， and inflammatory and immune system. The key genes of the PPI network were Fos， Epha8， Npy2r， Htr2c， and Nr4a1. ConclusionUnder the guidance of TCM theories of treatment based on syndrome differentiation and etiology and pathogenesis，this study established a depression model with yin deficiency and internal heat in animals and evaluation system in accordance with the symptoms and signs of emotional diseases， and further confirmed the scientificity of the modeling method and the underlying mechanism of BHDH in interfering with depression with Yin deficiency and internal heat based on the results of mRNA sequencing.

Treatment of Diabetic Depression with Traditional Chinese Medicine：A Review / 中国实验方剂学杂志

Diabetes and depression are both incurable chronic diseases， which are complementary and integrated. They are clinically called diabetic depression. A large number of epidemiological and clinical studies have confirmed that diabetes interacts with depression， leading to complex conditions of diabetic depression， difficult treatment， and poor prognosis. Diabetes and depression are considered two independent diseases in the majority of the existing clinical methods for the treatment of diabetic depression， with many defects such as low efficiency and severe side effects. Traditional Chinese medicine （TCM） treatment of diabetic depression， characterized by multiple targets， multiple pathways， and overall coordination， can adjust the synergy between multiple systems of the body and is advantageous in the treatment of diabetic depression. However， the evaluation of the efficacy of TCM in the treatment of diabetic depression is mostly limited to the improvement of clinical symptoms， the control of blood sugar level， and the score of depression scale， and there is a lack of in-depth research on the mechanism of action. Therefore， many researchers are devoted to exploring the underlying mechanism of TCM in the treatment of diabetes combined with depression. Clarifying the comorbidity mechanism is the key in treating diabetic depression. In this study， we made an introduction according to the mechanism based on the relevant research reports on the treatment of diabetic depression with TCM and summarized its specific mechanisms， including insulin resistance， oxidative stress and inflammation， and nervous system disorder. The interaction between the various mechanisms has further aggravated the complexity of diabetic depression. We have drawn a diagram of the mechanism pathways of diabetic depression in order to provide new ideas for clinical diagnosis and treatment.

Presegetane diterpenoids from Euphorbia sieboldiana as a new type of anti-liver fibrosis agents that inhibit TGF-ß/Smad signaling pathway.

Seven new diterpenoids, eupholenes A-G (1-7), including two presegetanes (1 and 2), four jatrophanes (3-6), and one paraliane (7), along with 19 known analogues (8-26) were obtained by anti-liver fibrosis bioassay-guided isolation of Euphorbia sieboldiana. Their structures were elucidated by extensive spectroscopic data analyses, chemical methods, ECD calculations, and single-crystal X-ray diffractions. Euphorbesulin A (10), a presegetane diterpenoid (5/9/5 ring system), was identified as a promising anti-liver fibrosis agent that could inhibit the expressions of fibronectin (FN), α-smooth muscle actin (α-SMA), and collagen I in TGF-ß1-stimulated LX-2 cells at a micromolar level. Mechanistic study revealed that 10 suppressed liver fibrosis via inhibition of TGF-ß/Smad signaling pathway, and its potential target was TGF-ß type I receptor. These findings suggested that presegetane diterpenoid could serve as a new type of structural motif in future anti-liver fibrosis drug development.

Haplotype-resolved genome assembly and allele-specific gene expression in cultivated ginger.

Ginger (Zingiber officinale) is one of the most valued spice plants worldwide; it is prized for its culinary and folk medicinal applications and is therefore of high economic and cultural importance. Here, we present a haplotype-resolved, chromosome-scale assembly for diploid ginger anchored to 11 pseudochromosome pairs with a total length of 3.1 Gb. Remarkable structural variation was identified between haplotypes, and two inversions larger than 15 Mb on chromosome 4 may be associated with ginger infertility. We performed a comprehensive, spatiotemporal, genome-wide analysis of allelic expression patterns, revealing that most alleles are coordinately expressed. The alleles that exhibited the largest differences in expression showed closer proximity to transposable elements, greater coding sequence divergence, more relaxed selection pressure, and more transcription factor binding site differences. We also predicted the transcription factors potentially regulating 6-gingerol biosynthesis. Our allele-aware assembly provides a powerful platform for future functional genomics, molecular breeding, and genome editing in ginger.

Euphorboside A, a cytotoxic meroterpenoid glycoside with an unusual humulene-phloroglucinol skeleton from Euphorbia kansuensis.

Euphorboside A (1), an unusual meroterpenoid glycoside featuring the incorporation of an acylphloroglucinol moiety into a humulene skeleton to form a 6/6/11 ring system, was isolated from the roots of Euphorbia kansuensis. Its structure was elucidated by extensive spectroscopic analysis, chemical methods, and ECD calculations. Compound 1 was screened for the cytotoxicity against nine cancer cell lines, and 1 showed marked inhibitory activities against human colon cancer RKO and human breast cancer MDA-MB-231 cell lines with IC50 values of 3.70 and 4.15 µM, respectively.

Archaeobotanical evidence of the use of medicinal cannabis in a secular context unearthed from south China.

ETHNOPHARMACOLOGICAL RELEVANCE: As one of the first plants used by ancient people, cannabis has been used for medicinal purposes for thousands of years. The long history of medicinal cannabis use contrasts with the paucity of archaeobotanical records. Moreover, physical evidence of medicinal cannabis use in a secular context is much rarer than evidence of medicinal cannabis use in religious or ritual activities, which impedes our understanding of the history of medicinal cannabis use. AIM OF THE STUDY: This study aims to provide archaeobotanical evidence of medicinal cannabis use and analyse the specific medicinal usage of cannabis in a secular context in ancient times. MATERIALS AND METHODS: Plant remains were collected from the Laoguanshan Cemetery of the Han Dynasty in Chengdu, South China, with the archaeological flotation process and were identified based on morphological and anatomical characteristics. The examination of the medicinal significance of the remains relied on the investigation of the documentation on unearthed medical bamboo slips, the diseases of the tomb occupants, the cemetery's cultural background and Chinese historical records. RESULTS: The botanical remains were accurately identified as cannabis. More than 120 thousand fruits were found, which represents the largest amount of cannabis fruit remains that have been statistically analysed from any cemetery in the world thus far. The cannabis fruits are suspected to have been used for medical purposes in a secular context and were most likely used to stop severe bleeding of the uterus and treat lumbago and/or arthralgia. CONCLUSIONS: The cannabis fruit remains reported here likely represent the first physical evidence of medicinal cannabis use for the treatment of metrorrhagia, severe lumbago, and/or arthralgia. This study emphasizes the importance of the evidence of the diseases suffered by the occupants of the tomb in determining the medicinal use of cannabis in a secular context and contributes to a comprehensive understanding of the ancient history of medicinal cannabis.

Dietary shifts and diversities of individual life histories reveal cultural dynamics and interplay of millets and rice in the Chengdu Plain, China during the Late Neolithic (2500-2000 cal. BC).

OBJECTIVES: We undertook a more comprehensive analyses than our previous study (Yi et al., International Journal of Osteoarchaeology, 2018, 28, 636-644) at the Gaoshan site (~2500-2000 cal. BC) to expand our understanding of the different roles of rice and millets to human subsistence strategies, diachronic shift of human diets, diversity of human life histories and cultural influence (dental ablation) to human population. MATERIALS AND METHODS: Carbon and nitrogen isotopic analyses of human (ribs and long bones, n = 68) and animal (n = 15) bones as well as carbonized seeds from rice and millets (n = 8) were undertaken. Human bones were directly AMS-14 C dated. In addition, sequential sampling of 16 individuals with varied age and sex and cultural contexts for isotopic analysis was also conducted. RESULTS: The calibrated dating results (n = 27) indicate that there existed two periods of occupation at the site, ~2500-2200 BC and ~2200-1900 BC. Moderate high δ15 N values were found in the crops. Isotopic data from bone collagen suggest that the humans mainly relied on C3 -based animal protein and were supplemented by C4 -based foods. This isotopic pattern is also seen in pigs. Significant difference of human δ13 C values (Mann-Whitney U test, p < 0.05) between the two periods was observed. Compared to the bones, the isotopic data of human dentine serial sections show a much wider variability and higher δ13 C values. DISCUSSION: The crops (millets and rice) were probably manured. Human individuals subsisted on rice/millet agriculture and pigs in general. In combination with the radiocarbon dates, the increase of C3 (rice) consumption by the humans was found from the early (2500-2200 cal. BC) to late (2200-2000 cal. BC) periods, indicating the intensification of rice agriculture through time. However, four categories of human life histories during childhood are identified given different isotopic profiles of dentine sections, demonstrating that C3 (rice) and C4 (millets)-based foods played different roles in human lives. Even though, there were similar weaning practices among the human populations. It is surprising that human individuals with dental ablation, cultural characteristic in the Middle and Lower Yangtze River Valley, consumed more millets during childhood in the early period than those without dental ablation in the late period. Our study here provides novel insights into cultural dynamics and the interplay between rice and millets in rice-millet agricultural system during the Late Neolithic in Southwest China.