Analysis on new research and development ideas and technical points of traditional Chinese medicine for prevention and treatment of chronic heart failure / 中国中药杂志

Chronic heart failure(CHF), a serious and end stage of various heart diseases, is a common chronic cardiovascular disease in the 21 st century. Literature data show that the 5-year mortality rate of hospitalized patients with heart failure is as high as 50%. Nowadays, the development of drugs treating heart failure has become a hot spot, meanwhile, traditional Chinese medicine(TCM) has shown the advantages in the treatment of chronic heart failure. In this article, four stages to develop traditional Chinese medicine for chronic heart failure were proposed. Firstly, discuss and screen ideas and methods with regard to the development of TCM and its prescriptions based on clinical needs. Secondly, study the preparation process and quality control method by referring to the existing clinical background of TCM prescriptions and analyzing the chemical compositions and pharmacological action characteristics of each herb in the prescription. Then, design non-clinical evaluation programs and carry out researches on pharmacodynamics and toxicology by combining the experience of clinical use of TCM prescriptions and future clinical positioning, and gradually adjust and improve the programs during implementation. Finally, conduct clinical trial application(IND) by submitting registration application data which are base on the clinical drug experience, preclinical research pharmacy, main pharmacodynamics, safety test results of the prescription, clinical positioning, and reasonable clinical trial plan designed by the theory of TCM. After passing the IND technical review, the clinical trial study shall be officially launched to achieve the desired results and obtain effective Chinese patent medicines for heart failure treatment.

Recent advances of traditional Chinese medicine on the prevention and treatment of COVID-19 / 中国天然药物

Coronavirus disease-2019 (COVID-19) is a new highly infectious disease caused by a novel coronavirus. Recently, the number of new cases infected pneumonia in the world continues to increase, which has aroused great concern from the international community. At present, there are no small-molecule specific anti-viral drugs for the treatment. The high mortality rate seriously threatens human health. Traditional Chinese medicine (TCM) is a unique health resource in China. The combination of TCM and Western medicine has played a positive and important role in combating COVID-19 in China. In this review, through literature mining and analysis, it was found that TCM has the potential to prevent and treat the COVID-19. Then, the network pharmacological studies demonstrated that TCM played roles of anti-virus, anti-inflammation and immunoregulation in the management of COVID-19 via multiple components acting on multiple targets and multiple pathways. Finally, clinical researches also confirmed the beneficial effects of TCM on the treatment of patients. This review may provide meaningful and useful information on further drug development of COVID-19 and other viral infectious diseases.

Research Progress on Amelioration of Hemorrhagic Stroke by Traditional Chinese Medicine / 中国实验方剂学杂志

Cerebral hemorrhage, also known as hemorrhagic stroke, refers to non-traumatic intracerebral hemorrhage. Cerebral hemorrhage is a common and frequently-occurring disease in middle-aged and elderly people. It has the characteristics of high mortality and high disability rate. Most survivors have serious neurological deficits, which seriously threaten human health and quality of life.The pathological process of cerebral hemorrhage is more complicated, including the formation and expansion of hematoma, elevated intracranial pressure, destruction of blood-brain barrier, brain edema, neuronal apoptosis and neurological dysfunction.At present, the main methods for treating cerebral hemorrhage by western medicine include antiplatelet therapy, blood pressure reduction and hematoma surgery. However, it is usually accompanied by the risk of rebleeding caused by surgery, infection, nerve damage and insufficient effective perfusion pressure. Chinese medicine believes that blood stasis and endogenous fever are the most basic pathogenesis of acute cerebral hemorrhage. The previous studies found that many traditional Chinese medicine(TCM) can improve blood-brain barrier damage, brain edema, neuronal apoptosis and neurological dysfunction related to cerebral hemorrhage to reduce cerebral hemorrhage injury. Main signal transduction pathways regulated by TCM to treat cerebral hemorrhageinclude Aquaporin 4(AQP4)-related, phosphatidylinositol-3-kinase/protein kinase B(PI3K/Akt), nuclear factor kappa B(NF-κB),suppressor protein 53/Bcl-2-associated X protein/Caspase-3(p53/Bax/Caspase-3)molecular pathways, etc.In this paper, based on the current Chinese medicine to improve the brain damage caused by cerebral hemorrhage and the molecular pathway of intervention, it reviews the research progress published in foreign journals in the past ten years, in order to provide clues and reference for the treatment of hemorrhagic stroke diseases and and the further development of new drugs.

Advances in the antitumor activities and mechanisms of action of steroidal saponins / 中国天然药物

The steroidal saponins are one of the saponin types that exist in an unbound state and have various pharmacological activities, such as anticancer, anti-inflammatory, antiviral, antibacterial and nerves-calming properties. Cancer is a growing health problem worldwide. Significant progress has been made to understand the antitumor effects of steroidal saponins in recent years. According to reported findings, steroidal saponins exert various antitumor activities, such as inhibiting proliferation, inducing apoptosis and autophagy, and regulating the tumor microenvironment, through multiple related signaling pathways. This article focuses on the advances in domestic and foreign studies on the antitumor activity and mechanism of actions of steroidal saponins in the last five years to provide a scientific basis and research ideas for further development and clinical application of steroidal saponins.

Advances in the antitumor activities and mechanisms of action of steroidal saponins / 中国天然药物

The steroidal saponins are one of the saponin types that exist in an unbound state and have various pharmacological activities, such as anticancer, anti-inflammatory, antiviral, antibacterial and nerves-calming properties. Cancer is a growing health problem worldwide. Significant progress has been made to understand the antitumor effects of steroidal saponins in recent years. According to reported findings, steroidal saponins exert various antitumor activities, such as inhibiting proliferation, inducing apoptosis and autophagy, and regulating the tumor microenvironment, through multiple related signaling pathways. This article focuses on the advances in domestic and foreign studies on the antitumor activity and mechanism of actions of steroidal saponins in the last five years to provide a scientific basis and research ideas for further development and clinical application of steroidal saponins.

Advances of active ingredients of traditional Chinese medicine in the preven-tion and treatment of osteoarthritis / 中国药科大学学报

Osteoarthritis (OA),a common chronic degenerative joint disease,rises gradually with age,which seri-ously affects the quality of life of middle-aged and elderly patients. Currently,the therapeutic medications such as nonsteroidal anti-inflammatory drugs (NSAIDs)and analgesics might improve OA symptoms,but cannot prevent the development of OA. The active ingredients of traditional Chinese medicine (TCM)have unique advantages in the treatment of OA. This article reviews the research progress of active ingredients of TCM in the prevention and treatment of OA reported by domestic and foreign journals in the past five years from the aspects of inhibition of the secretion of inflammation-related factors,improvement of cartilage matrix synthesis and catabolic imbalance, inhibition of chondrocyte apoptosis,promotion of chondrocyte proliferation,and regulation of estrogen levels,with an attempt to provide a theoretical basis for the development of new drugs for OA.

Ge-Gen Decoction attenuates oxytocin-induced uterine contraction and writhing response: potential application in primary dysmenorrhea therapy / 中国天然药物

The uterine tetanic contraction and uterine artery blood flow reduction are possible reasons for primary dysmenorrhea (PD). In the present study, we aimed to evaluate the uterine relaxant effect and the influence on uterine artery blood velocity of Ge-Gen Decoction (GGD), a well-known Chinese herbal formula. In female ICR mice, uterine contraction was induced by oxytocin exposure following estradiol benzoate pretreatment, and the uterine artery blood velocity was detected by Doppler ultrasound. Histopathological examination of the uterine tissue samples were performed by H&E staining. Ex vivo studies demonstrated that oxytocin, posterior pituitary, or acetylcholine induced contractions in isolated mouse uterus. GGD inhibited both spontaneous and stimulated contractions. In vivo study demonstrated that GGD significantly reduced oxytocin-induced writhing responses with a maximal inhibition of 87%. Further study demonstrated that GGD normalized oxytocin-induced abnormalities of prostaglandins F2 alpha (PGF2α) and Ca(2+) in mice. In addition, injection of oxytocin induced a decrease in uterine artery blood flow velocity. Pretreatment with GGD reversed the oxytocin response on blood flow velocity. Histopathological examination showed pretreatment with GGD alleviated inflammation and edema in the uterus when compared with the model group. Both ex vivo and in vivo results indicated that GGD possessed a significant spasmolytic effect on uterine tetanic contraction as well as improvement on uterine artery blood velocity which may involve PGF2α and Ca(2+) signaling, suggesting that GGD may have a clinic potential in PD therapy.

A combination of four effective components derived from Sheng-mai san attenuates hydrogen peroxide-induced injury in PC12 cells through inhibiting Akt and MAPK signaling pathways / 中国天然药物

The present study was designed to investigate whether a combination of four effective components derived from Sheng-mai san (SMXZF; ginsenoside Rb1: ginsenoside Rg1: DT-13: Schizandrol A as 6 : 9 : 4 : 5) could attenuate hydrogen peroxide (H2O2)-induced injury in PC12 cells, focusing on the Akt and MAPK pathways . The PC12 cells were exposed to H2O2 (400 μmol·L(-1)) for 1 h in the presence or absence of SMXZF pre-treatment for 24 h. Cell viability was measured by MTT assay. The efflux of lactate dehydrogenase (LDH), the intracellular content of malondialdehyde (MDA), the activities of superoxide dismutase (SOD), and caspase-3 were also determined. Cell apoptosis was measured by Hoechst 33342 staining and Annexin V-FITC/PI staining method. The expression of Bcl-2, Bax, cleaved caspase-3, Akt, and MAPKs were detected by Western blotting analyses. SMXZF pretreatment significantly increased the cell viability and SOD activity and improved the cell morphological changes, while reduced the levels of LDH and MDA at the concentrations of 0.1, 1 and 10 μg·mL(-1). SMXZF also inhibited H2O2-induced apoptosis in PC12 cells. Moreover, SMXZF reduced the activity of caspase-3, up-regulated the protein ratio of Bcl-2 and Bax and inhibited the expression of cleaved caspase-3, p-Akt, p-p38, p-JNK and p-ERK1/2 in H2O2-induced PC12 cells. Co-incubation of Akt inhibitor or p38 inhibitor partly attenuated the protection of SMXZF against H2O2-injured PC12 cells. In conclusion, our findings suggested that SMXZF attenuated H2O2-induced injury in PC12 cells by inhibiting Akt and MAPKs signaling pathways, which might shed insights on its neuroprotective mechanism.

An optimized micro-assay of myosin II ATPase activity based on the molybdenum blue method and its application in screening natural product inhibitors / 中国天然药物

Myosin II plays multiple roles in physiological and pathological functions through its ATPase activity. The present study was designed to optimize a micro-assay of myosin II ATPase activity based on molybdenum blue method, using a known myosin II ATPase inhibitor, blebbistatin. Several parameters were observed in the enzymatic reaction procedure, including the concentrations of the substrate (ATP) and calcium chloride, pH, and the reaction and incubation times. The proportion of coloration agent was also investigated. The sensitivity of this assay was compared with the malachite green method and bioluminescence method. Additionally, 20 natural compounds were studied for myosin II ATPase inhibitory activity using the optimized method. Our results showed that ATP at the concentration of 5 mmol·L(-1) and ammonium molybdate : stannous chloride at the ratio of 15 : 1 could greatly improve the sensitivity of this method. The IC50 of blebbistatin obtained by this method was consistent with literature. Compound 8 was screened with inhibitory activity on myosin II ATPase. The optimized method showed similar accuracy, lower detecting limit, and wider linear range, which could be a promising approach to screening myosin II ATPase inhibitors in vitro.

Quantitative analysis of seven phenolic acids in eight Yinqiao Jiedu serial preparations by quantitative analysis of multi-components with single-marker / 药学学报

The study aims to develop a unified method to determine seven phenolic acids (neochlorogenic acid, chlorogenic acid, 4-caffeoylquinic acid, caffeic acid, isochlorogenic acid B, isochlorogenic acid A and isochlorogenic acid C) contained in honeysuckle flower that is the monarch drug of all the eight Yinqiao Jiedu serial preparations using quantitative analysis of multi-components by single-marker (QAMS). Firstly, chlorogenic acid was used as a reference to get the average relative correction factors (RCFs) of the other phenolic acids in ratios to the reference; columns and instruments from different companies were used to validate the durability of the achieved RCFs in different levels of standard solutions; and honeysuckle flower extract was used as the reference substance to fix the positions of chromatographic peaks. Secondly, the contents of seven phenolic acids in eight different Yinqiao Jiedu serial preparations samples were calculated based on the RCFs durability. Finally, the quantitative results were compared between QAMS and the external standard (ES) method. The results have showed that the durability of the achieved RCFs is good (RSD during 0.80% - 2.56%), and there are no differences between the quantitative results of QAMS and ES (the relative average deviation < 0.93%). So it can be successfully used to the quantitative control of honeysuckle flower principally prescribed in Yinqiao Jiedu serial preparations.

Effects of Danggui-Shaoyao-San on the Influence of Spatial Learning and Memory Induced by Experimental Tooth Movement / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The pain caused by orthodontic treatment has been considered as tough problems in orthodontic practice. There is substantial literature on pain which has exactly effected on learning and memory; orthodontic tooth movement affected the emotional status has been showed positive outcomes. Danggui-Shaoyao-San (DSS) is a Traditional Chinese Medicine prescription that has been used for pain treatment and analgesic effect for orthodontic pain via inhibiting the activations of neuron and glia. We raised the hypothesis that DSS could restore the impaired abilities of spatial learning and memory via regulating neuron or glia expression in the hippocampus.</p><p><b>METHODS</b>A total of 36 rats were randomly divided into three groups: (1) Sham group (n = 12), rats underwent all the operation procedure except for the placement of orthodontic forces and received saline treatment; (2) experimental tooth movement (ETM) group (n = 12), rats received saline treatment and ETM; (3) DSS + ETM (DETM) group (n = 12), rats received DSS treatment and ETM. All DETM group animals were administered with DSS at a dose of 150 mg/kg. Morris water maze test was evaluated; immunofluorescent histochemistry was used to identify astrocytes activation, and immunofluorescent dendritic spine analysis was used to identify the dendritic spines morphological characteristics expression levels in hippocampus.</p><p><b>RESULTS</b>Maze training sessions during the 5 successive days revealed that ETM significantly deficits in progressive learning in rats, DSS that was given from day 5 prior to ETM enhanced progressive learning. The ETM group rats took longer to cross target quadrant during the probe trial and got less times to cross-platform than DETM group. The spine density in hippocampus in ETM group was significantly decreased compared to the sham group. In addition, thin and mature spine density were decreased too. However, the DSS administration could reverse the dendritic shrinkage and increase the spine density compared to the ETM group. Astrocytes activation showed the opposite trend in hippocampus dentate gyrus (DG).</p><p><b>CONCLUSIONS</b>Treatment with DSS could restore the impaired abilities on ETM-induced decrease of learning and memory behavior. The decreased spines density in the hippocampus and astrocytes activation in DG of hippocampus in the ETM group rats may be related with the decline of the ability of learning and memory. The ability to change the synaptic plasticity in hippocampus after DSS administration may be correlated with the alleviation of impairment of learn and memory after ETM treatment.</p>

Novel cytotoxic steroidal glycosides from the roots of Liriope muscari / 中国天然药物

The present study was designed to investigate the chemical constituents and bioactivities of the roots of Liriope muscari (Decne.) L.H. Bailey. The compounds were isolated through various chromatography techniques, including silica gel, Sephadex LH-20, and semi-preparative HPLC. The structures were elucidated by infrared (IR), mass spectrometric (MS), 1D- and 2D-NMR analyses in comparison with reference data. In addition, the cytotoxicity of these compounds against human breast cancer MDA-MB-435 cells was evaluated by the MTT assay. Two new steroidal glycosides, 25(R, S)-ruscogenin-1-O-[β-D-fucopyranosyl (1→2)]-[β-D-xylopyranosyl(1→3)]β-D-glucopyranoside (Liriopem I, 1) and 25(R, S)- ruscogenin-1-O-[β-D-fucopyranosyl (1→2)]-[β-D-xylopyranosyl(1→4)]-β-D-fucopyranoside (Liriopem II, 2 and two known compounds LM-S6 (3) and DT-13 (4) were isolated and identified. Liriopem I(1), liriopem II(2) and DT-13 (4) showed remarkable cytotoxicity with IC50 values being (0.58 ± 0.08), (0.05 ± 0.10), and (0.15 ± 0.09) μg·mL(-1), respectively. In summary, compounds 1 and 2 identified in the present study exerted cytotoxicity against breast cancer cells, providing a basis for future development of these compounds as novel anticancer agents.

Advances in the pharmacological activities and mechanisms of diosgenin / 中国天然药物

Diosgenin, a well-known steroid sapogenin derived from plants, has been used as a starting material for production of steroidal hormones. The present review will summarize published literature concerning pharmacological potential of diosgenin, and the underlying mechanisms of actions. Diosgenin has shown a vast range of pharmacological activities in preclinical studies. It exhibits anticancer, cardiovascular protective, anti-diabetes, neuroprotective, immunomodulatory, estrogenic, and skin protective effects, mainly by inducing apoptosis, suppressing malignant transformation, decreasing oxidative stress, preventing inflammatory events, promoting cellular differentiation/proliferation, and regulating T-cell immune response, etc. It interferes with cell death pathways and their regulators to induce apoptosis. Diosgenin antagonizes tumor metastasis by modulating epithelial-mesenchymal transition and actin cytoskeleton to change cellular motility, suppressing degradation of matrix barrier, and inhibiting angiogenesis. Additionally, diosgenin improves antioxidant status and inhibits lipid peroxidation. Its anti-inflammatory activity is through inhibiting production of pro-inflammatory cytokines, enzymes and adhesion molecules. Furthermore, diosgenin drives cellular growth/differentiation through the estrogen receptor (ER) cascade and transcriptional factor PPARγ. In summary, these mechanistic studies provide a basis for further development of this compound for pharmacotherapy of various diseases.

Sheng-Mai-San attenuates contractile dysfunction and structural damage induced by chronic intermittent hypoxia in mice / 中国天然药物

Sheng-Mai-San (SMS), a well-known Chinese medicinal plant formula, is widely used for the treatment of cardiac diseases characterized by deficiency of Qi and Yin syndrome. A mouse chronic intermittent hypoxia (CIH) model was established to mimic the primary clinical features of deficiency of Qi and Yin syndrome. Mice experienced CIH for 28 days (nadir 7% to peak 8% oxygen, 20 min per day), resulting in left ventricle (LV) dysfunction and structure abnormalities. After administration of SMS (0.55, 1.1, and 5.5 g·kg(-1)·d(-1)) for four weeks, improved cardiac function was observed, as indicated by the increase in the ejection fraction from the LV on echocardiography. SMS also preserved the structural integrity of the LV against eccentric hypotrophy, tissue vacuolization, and mitochondrial injury as measured by histology, electron microscopy, and ultrasound assessments. Mechanistically, the antioxidant effects of SMS were demonstrated; SMS was able to suppress mitochondrial apoptosis as indicated by the reduction of several pro-apoptotic factors (Bax, cytochrome c, and cleaved caspase-3) and up-regulation of the anti-apoptosis factor Bcl-2. In conclusion, these results demonstrate that SMS treatment can protect the structure and function of the LV and that the protective effects of this formula are associated with the regulation of the mitochondrial apoptosis pathway.

Network pharmacology-based prediction and verification of the molecular targets and pathways for schisandrin against cerebrovascular disease / 中国天然药物

AIM@#To illuminate the molecular targets for schisandrin against cerebrovascular disease based on the combined methods of network pharmacology prediction and experimental verification.@*METHOD@#A protein database was established through constructing the drug-protein network from literature mining data. The protein-protein network was built through an in-depth exploration of the relationships between the proteins. The computational platform was implemented to predict and extract the sensitive sub-network with significant P-values from the protein-protein network. Then the key targets and pathways were identified from the sensitive sub-network. The most related targets and pathways were also confirmed in hydrogen peroxide (H2O2)-induced PC12 cells by Western blotting.@*RESULTS@#Twelve differentially expressed proteins (gene names: NFKB1, RELA, TNFSF10, MAPK1, CHUK, CASP8, PIGS2, MAPK14, CREB1, IFNG, APP, and BCL2) were confirmed as the central nodes of the interaction network (45 nodes, 93 edges). The NF-κB signaling pathway was suggested as the most related pathway of schisandrin for cerebrovascular disease. Furthermore, schisandrin was found to suppress the expression and phosphorylation of IKKα, as well as p50 and p65 induced by H2O2 in PC12 cells by Western blotting.@*CONCLUSION@#The computational platform that integrates literature mining data, protein-protein interactions, sensitive sub-network, and pathway results in identification of the NF-κB signaling pathway as the key targets and pathways for schisandrin.

Diosgenin inhibits tumor necrosis factor-induced tissue factor activity and expression in THP-1 cells via down-regulation of the NF-κB, Akt, and MAPK signaling pathways / 中国天然药物

AIM@#To investigate whether diosgenin could modulate tissue factor (TF) procoagulation activity, expression, and related signal transduction pathways.@*METHODS@#Human THP-1 monocytic cells were exposed to tumor necrosis factor-α (TNF-α, 10 ng·mL(-1)) with or without diosgenin (0.01, 0.1, and 1 μmol · L(-1)) for 2 h or 5 h to induce TF procoagulant activity and expression, which were determined by the simplified chromogenic assay, reverse transcription-polymerase chain reaction (RT-PCR), real-time quantitative PCR, and Western blotting assays. In addition, the activation of the NF-κB, Akt, and MAPK signaling pathways were also measured by Western blotting.@*RESULTS@#Diosgenin significantly inhibited TNF-α-induced TF procoagulant activity at concentrations of 0.01 to 1 μmol · L(-1) with IC50 of 0.25 μmol · L(-1). It also reduced protein expression and mRNA accumulation of TF dose-dependently in activated THP-1 cells. TNF-α stimulated significantly phosphorylation on Ser536 of NF-κB/p65, Ser473 of Akt at 5-15 min, and activations of IKK-β and ERK at 15-30 min. Diosgenin (1 μmol · L(-1)) could inhibit the phosphorylation of NF-κB/p65, IKK-β, Akt, ERK, and JNK, but had no remarkable effects on IκB and p38 phosphorylation in THP-1 cells.@*CONCLUSION@#Diosgenin inhibits TNF-α-induced TF activity and expression in monocytes, partly due to its down-regulation of the phosphorylation of NF-κB/p65, IKK-β, Akt, ERK, and JNK.