[Qualitative and semiquantitative analyses of the chemical components of the seed coat and kernel of Ziziphi Spinosae Semen].

Ziziphi Spinosae Semen refers to the dried seed of Ziziphus jujuba Mill. var. spinosa (Bunge) Hu ex H. F. Chou. The seed is composed of a reddish brown coat and a yellow kernel. A comparative study was conducted to investigate differences in the chemical composition and their relative contents between the seed coat and kernel of Ziziphi Spinosae Semen. First, the chemical compounds found in the seed coat and kernel were characterized and identified using ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS). The analytical results tentatively identified 57 chemical compounds based on reference-compound comparison, literature retrieval, and chemical-database (e. g., MassBank) searches; these compounds included 14 triterpenes, 23 flavonoids, 7 alkaloids, 6 carboxylic acids, and 7 other types of compounds. The mass error of the identified compounds was within the mass deviation range of 5×10-6 (5 ppm). Next, two methods of multivariate statistical analysis, namely, principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA), were used to compare the differential compounds between the two seed parts. A total of 17 differential compounds were screened out via OPLS-DA based on a variable importance in projection (VIP) value of >5. The results revealed that betulinic acid, betulonic acid, alphitolic acid, and jujuboside Ⅰ mainly existed in the seed coat whereas the 13 other compounds, such as spinosin, jujuboside A, and 6‴-feruloylspinosin, mainly existed in the seed kernel. Therefore, these 17 differential compounds can be used to distinguish between the two seed parts. Finally, a semiquantitative method was established using UPLC and a charged aerosol detector (CAD) with inverse gradient compensation in the mobile phase. Six representative compounds with different types were selected to examine the CAD response consistency: magnoflorine (alkaloid), spinosin (flavone), 6‴-feruloylspinosin (flavone), jujuboside A (triterpenoid saponin), jujuboside B (triterpenoid saponin), and betulinic acid (triterpenoid acid). The results showed that the relative standard deviation (RSD) of the average response factors at different levels of these six compounds was 7.04% and that their response intensities were similar. Moreover, each compound in the fingerprint demonstrated good response consistency, and the peak areas obtained directly reflected the contents of each compound. Based on the semiquantitative fingerprints obtained, betulinic acid and oleic acid were considered the main components of the seed coat. The betulinic acid content in the seed coat was approximately 7 times higher than that in the seed kernel. Spinosin, jujuboside A, linoleic acid, betulinic acid, and oleic acid were the main components of the seed kernel. The spinosin content in the seed kernel was 18 times higher than that in the seed coat. In addition, the jujuboside A content in the seed kernel was 24 times higher than that in the seed coat. The proposed method can accurately determine the main components and compare the relative contents of these components in different seed parts. In summary, this study identified the differences in chemical components between the seed coat and kernel of Ziziphi Spinosae Semen and clarified the main components and their relative contents in these parts. The findings can not only provide a basis for the identification of chemical compounds and quality research on different parts of Ziziphi Spinosae Semen but also promote the development and utilization of this traditional Chinese medicine.

Association of traditional Chinese medicine body constitution and cold syndrome with leukocyte mitochondrial functions: An observational study.

Body constitution in traditional Chinese medicine (TCM) refers to the holistic and relatively durable state of an individual, based on the qi and blood assessment, and TCM syndrome is defined as the theoretical abstraction of disease-symptom profiles. The biological basis as related to mitochondria, which produce most of the cellular energy, has not been well studied. This study aimed to elucidate the association of mitochondrial function with TCM body constitution and cold syndrome. Body constitution and cold syndrome in TCM were assessed using the Constitution in Chinese Medicine Questionnaire (CCMQ). The mitochondrial function of peripheral leukocytes was evaluated based on oxygen consumption rate (OCR) and enzyme activity; OCR reflects mitochondrial activity and the capacity to produce adenosine triphosphate (ATP). Cellular adenosine nucleotides and malondialdehyde levels were determined using high-performance liquid chromatography to assess the potential bioenergetic mechanisms. A total of 283 adults participated in this study. Leukocytes from subjects with a balanced constitution had higher OCRs than those with unbalanced constitutions. Yang deficiency and cold syndrome also demonstrated lower energy metabolism, as indicated by reduced basal metabolic rate and cellular levels of ATP and malondialdehyde. Decreased mitochondrial enzyme activity has been observed in individuals with the cold syndrome. Unbalanced body constitutions in TCM impair mitochondrial function in leukocytes, which may contribute to the high disease susceptibility. Cold syndrome is characterized by reduced mitochondrial mass, which may explain its symptoms of low-energy metabolism and cold intolerance.

[Discussion on safety evaluation and risk control measures of Epimedii Folium].

Epimedii Folium,a commonly used traditional Chinese medicine,has the effect of tonifying kidney Yang,strengthening bones and treating rheumatism. However,in recent years,the number of reports on adverse reactions of Epimedii Folium and its Chinese patent medicines such as Xianling Gubao Capsules and Zhuanggu Guanjie Pills has been gradually increased,and the toxicity of Epimedii Folium has attracted more and more attention. In this article,the ancient and modern literature on Epimedii Folium was traced through a comprehensive and systematic literature analysis method. According to the 2015 edition of the Chinese Pharmacopoeia,Epimedii Folium refers to the dried leaves of Epimedii Folium brevicomu,E. sugittutum,E. pubescens or E. koreuuum. The Chinese Pharmacopoeia also includes E. wushanense of Wushan Epimedium,which is the same plant variety as Epimedium. The study showed that there were differences in the geographical distribution,composition and toxicity among five species of Epimedium. This paper also explained the toxicity mechanism as well as efficacy enhancing and toxicity reducing effects of Epimedii Folium,and reported its related adverse reaction cases. Through a retrospective comparative study on the toxicity of the modern Chinese patent medicines Xianling Gubao Capsules and Zhuanggu Guanjie Pills containing Epimedii Folium,it was believed that Epimedii Folium had cardiovascular system toxicity,neurotoxicity,hepatotoxicity,long-term toxicity,acute toxicity,genotoxicity and special toxicity; its safe medication factors included patient syndrome,doctor factors,drug factors,processing and compatibility factors. Meanwhile,strategies were proposed to improve patient safety medication awareness,standardize Epimedii Folium varieties and quality supervision,and the toxicity of Epimedii Folium was studied,hoping to draw attention from scholars to the safety of Epimedii Folium,improve the safe use of Epimedii Folium,and prevent adverse reactions.

Comparison of hypoglycemic effects of ripened pu-erh tea and raw pu-erh tea in streptozotocin-induced diabetic rats.

Pu-erh tea is produced from the leaves of large-leaf tea species (Camellia sinensis var. assamica) in the Yunnan province of China and divided into ripened pu-erh tea (RIPT, with pile-fermentation) and raw pu-erh tea (RAPT) according to processing methods. RIPT extract showed more potent anti-diabetic effects on two-hour postprandial blood glucose (2h-PBG) and fasting blood glucose (FBG) than RAPT extract. UHPLC-Q-TOF/MS and UHPLC-PDA analyses found that 17 newly formed components and the increased components after fermentation, such as quinic acid, gallic acid, caffeine, puerin I and so on, might be the main contributors to the enhanced activities of RIPT. In addition, the probiotic role of RIPT to some beneficial gut bacteria, such as lactobacillus, Prevotellaceae NK3B31 group, Alloprevotella and Prevotella, was observed in our study. These results might provide a clue to anti-diabetic mechanism and active components of pu-erh tea, and use as a functional beverage worth to be further studied.

[Safety evaluation and risk control measures for Aconiti Kusnezoffii Radix].

Through the comprehensive and systematic research of domestic and overseas literature and information, we studied ancient original records on Aconiti Kusnezoffii Radix and its toxicity, analyzed related adverse cases and the animal toxicity experiments in recent years, then systematically analyzed the safety of Aconitum and its preparations, and finally we summarized the clinical characteristics and potential risk factors related to the safety of Aconitum. A report on adverse events of Aconitum in 76 patients with myocardial damage and renal damage accounting for 53.9% and 42.1% respectively, indicated that the safety problems of Aconitum may be related to heart toxicity and liver-kidney toxicity. Aconitum had complex compositions, and based on the animal experiments, Aconitum decoction had the highest toxicity at 2 h, and it reduced significantly at 4 h, which showed that the toxic components mainly depend on the hydrolysis or the decomposition degree of diester diterpenoid alkaloids. According to the toxicity study, Aconitum toxicity might occur in cardiovascular system, nervous system, kidney, embryo, reproductive system, and it was contraindicated in pregnant women. So far, specific antidote for aconitine poisoning is still a blank. The key for treatment is to correct arrhythmia timely and effectively, maintain stable vital signs, and meanwhile, give gastric lavage, intravenous fluid infusion and other therapies. So we suggest that the basic study for Aconitum toxicology should be strengthened, and the pharmacology and mechanism of toxicity, as well as the mechanism of processing for raising efficiency and reducing toxicity, should be further clarified to determine the quantity-effect relationship and eliminate safety hazards in using Aconitum.

Understanding Qi Running in the Meridians as Interstitial Fluid Flowing via Interstitial Space of Low Hydraulic Resistance.

Qi, blood and the meridians are fundamental concepts in Chinese medicine (CM), which are components of the human body and maintain physiological function. Pathological changes of qi, blood and meridians may lead to discomfort and disease. Treatment with acupuncture or herbal medicine aims to regulate qi and blood so as to recover normal function of the meridians. This paper explores the nature of qi as well as compares and correlates them with the structures of the human body. We propose a conceptualization of qi as being similar to the interstitial fluid, and the meridians as being similar to interstitial space of low hydraulic resistance in the body. Hence, qi running in the meridians can be understood as interstitial fluid flowing via interstitial space of low hydraulic resistance.

Effect of astragalus injection on renal tubular epithelial transdifferentiation in type 2 diabetic mice.

BACKGROUND: Astragalus injection is used by practitioners of traditional Chinese medicine to treat diabetic nephropathy (DN). The current study was conducted to determine the effect of astragalus on tubular epithelial transdifferentiation during the progression of DN in KKAy mice, as well as to investigate the molecular mechanism underlying this effect. METHODS: Diabetic, 14-week-old, male KKAy mice were randomly divided into a model group and an astragalus treatment group, while age-matched male C57BL/6 J mice were selected as controls. The treatment group received daily intraperitoneal injections of astragalus (0.03 mL/10 g per day), while the model group received injections of an equal volume of saline. Mice were euthanized after 24 weeks. Serum samples were obtained from the animals in each group for blood glucose measurement. Kidney tissue samples were used for morphometric studies. The mRNA and protein expression levels of transforming growth factor beta 1 (TGF-ß1), transforming growth factor beta receptor 1 (TGFß-R1), alpha smooth muscle actin (α-SMA), and E-cadherin were evaluated using real-time polymerase chain reaction (PCR) and western blotting. RESULTS: Astragalus significantly reduced blood glucose levels; inhibited morphological changes in the kidneys of KKAy mice; reduced mRNA and protein expression levels of TGF-ß1, TGFß-R1, and α-SMA; and increased E-cadherin expression. CONCLUSIONS: Tubular epithelial transdifferentiation plays an important role in the development of DN in diabetic mice. Administration of astragalus likely prevents or mitigates DN by suppressing tubular epithelial transdifferentiation, protecting KKAy mice from renal damage.

Steroidal Saponins from the Rhizomes of Aspidistra typica.

Eleven new furostanol saponins, typaspidosides B-L (1-11), one new spirostanol saponin, typaspidoside M (12), and five known spirostanol saponins, 25S-atropuroside (13), neoaspidistrin (14), (25S)-pratioside D1 (15), 25S-aspidistrin (16) and 25S-neosibiricoside (17) were isolated from the rhizomes of Aspidistra typica Baill. The structures of the new compounds were established using 1D and 2D NMR (1H-1H COSY, HMQC, HMBC and ROESY) spectroscopy, high resolution mass spectrometry, and chemical methods. The aglycones of 1-3 (unusual furostanol saponins with opened E ring type), 9 and 10 (the methoxyl substituent at C-23 position) were found, identified from natural products for the first time. Moreover, the anti-HIV activities of the isolated steroidal glycosides were assessed, and compounds 13, 14, 16 and 17 exhibited high active against HIV-1.

Effects of astragalus injection on the TGFß/Smad pathway in the kidney in type 2 diabetic mice.

BACKGROUND: In traditional Chinese medicine, astragalus injection is used to treat diabetic nephropathy (DN). The current study was conducted to determine the effects of astragalus injection on DN by assessing potential modulation of the transforming growth factor beta TGFß/Smad signaling pathway. METHODS: Diabetic, male KKAy mice, aged 14 weeks were randomly divided into a model group and an astragalus treatment group, while age-matched male C57BL/6J mice were selected as controls. The treatment group received daily intraperitoneal injections of astragalus (0.03 ml/10 g.d), while the model group received injections of an equivalent volume of saline. Mice were euthanized after 24 weeks. Serum samples were obtained from animals in each group, and blood glucose, creatinine, and urea nitrogen levels were measured. Tissue samples from the kidney were used for morphometric studies. The expression of TGFß1, TGFßR-Ι, Smad3, and Smad7 were evaluated using reverse transcription-polymerase chain reaction (RT-PCR), and western blot analysis. RESULTS: Mice in the model group became obese, and suffered complications, including hyperglycemia, polyuria, and proteinuria. Astragalus treatment significantly reduced albuminuria, improved renal function, and ameliorated changes in renal histopathology. Moreover, administration of astragalus injection increased Smad7 expression, and inhibited the expression of TGFßR-Ι, Smad3 and its phosphorylation, and decreased the mRNA level of TGFß1. CONCLUSIONS: The TGFß/Smad signaling pathway plays an important role in the development of DN. Administration of astragalus injection could prevent or mitigate DN by rebalancing TGFß/Smad signaling, and could play a protective role in DN-induced renal damage in KKAy mice.

[Effect of Wenmaitong on adhesion of monocytes to vascular endothelial cell induced by hyperlipidemic serum].

OBJECTIVE: To study the effect of Wenmaitong (WMT) and its disassembled formulas on the adhesion of monocytes to endothelial cells induced by hyperlipidemic serum to explore the mechanism of WMT on early arteriosclerosis obliterans (ASO). METHODS: Serums containing whole WMT and its disassembled formulas, including the formula consisted of warming Jing and boosting qi part (Wenjin Yiqi, WY) and that of promoting blood circulation part (Huoxue Tongmai, HT), as well as the serum contained high concentration of lipids were prepared conventionally, respectively. The adhesion of monocytes cell strain THP-1 to human umbilical vascular endothelial cells (HUVEC) was determined by rose bengal stain method, and ELISA was used to detect expressions of intercellular adhesion molecule (ICAM-1), vascular cellular adhesion molecule (VCAM-1) and P-selectin on HUVEC surface. RESULTS: WMT could inhibit THP-1 to HUVEC adhesion induced by hyperlipidemic serum, and down-regulate the expression of ICAM-1, VCAM-1, P-selectin on HUVEC surface, the two disassembled formulas could down-regulate different adhesion molecules. CONCLUSION: One mechanism of WMT on ASO may be its inhibition on arteriosclerosis by way of down-regulating the expression of vascular endothelial cells adhesion molecules to decrease the adhesion of monocyte to VEC, therefore to inhibit the monocytes migrating into vascular intima to develop foam cells.