LC-MS based metabonomics study on protective mechanism of ESWW in cerebral ischemia via CYTC/Apaf-1/NDRG4 pathway.

BACKGROUND: Ershiwuwei Zhenzhu pills was originally recorded in the Tibetan medical book Si Bu Yi Dian in the 8th century AD and is now included in the Pharmacopoeia of the People's Republic of China (2020). The pills can calm the nerves and open the mind as well as treat cerebral ischemia reperfusion injury, stroke, hemiplegia. However, its quality standards have not yet been established, and the therapeutic effect on cerebral ischemia by regulating the mitochondrial apoptosis pathway has not been elucidated. STUDY DESIGN AND METHODS: LC-MS was used to establish quality standards for Ershiwuwei Zhenzhu pills. Metabonomics, molecular docking, neuroethology, cerebral infarction ratio, pathological detection of diencephalon, cortex, and hippocampus, and molecular biology techniques were used to reveal the mechanism of the pills in regulating the mitochondrial apoptosis pathway to treat cerebral ischemia. RESULTS: The contents of 20 chemical components in Ershiwuwei Zhenzhu pills from 12 batches and 8 manufacturers was determined for the first time. Eleven differential metabolites and three metabolic pathways, namely, fructose and mannose metabolism, glycerophospholipid metabolism, and purine metabolism, were identified by metabonomics. The pills improved the neuroethology abnormalities of MCAO rats and the pathological damage in the diencephalon and decreased the ratio of cerebral infarction. It also significantly reduced the mRNA expression of AIF, Apaf-1, cleared caspase8, CytC, and P53 mRNA in the brain tissue and the protein expression of Apaf-1 and CYTC and increased the protein expression of NDRG4. CONCLUSION: In vitro quantitative analysis of the in vitro chemical components of Ershiwuwei Zhenzhu pills has laid the foundation for improving its quality control. The potential mechanism of the pills in treating cerebral ischemia may be related to the Apaf-1/CYTC/NDRG4 apoptosis pathway. This work provides guidance for clinical drug use for patients.

Qualitative and quantitative analyses of chemical constituents in vitro and in vivo and systematic evaluation of the pharmacological effects of Tibetan medicine Zhixue Zhentong capsules.

Introduction: Zhixue Zhentong capsules (ZXZTCs) are a Tibetan medicine preparation solely composed of Lamiophlomis rotata (Benth.) Kudo. L. rotata is the only species of the genus Laniophlomis (family Lamiaceae) that has medicinal constituents derived from the grass or root and rhizome. L. rotata is one of the most extensively used folk medicines by Tibetan, Mongolian, Naxi, and other ethnic groups in China and has been listed as a first-class endangered Tibetan medicine. The biological effects of the plant include hemostasis, analgesia, and the removal of blood stasis and swelling. Purpose: This study aimed to profile the overall metabolites of ZXZTCs and those entering the blood. Moreover, the contents of six metabolites were measured and the hemostatic, analgesic, and anti-inflammatory effects of ZXZTCs were explored. Methods: Ultra-performance liquid chromatography-tandem quadrupole time-of-flight high-resolution mass spectrometry (UPLC-Q-TOF-MS) was employed for qualitative analysis of the metabolites of ZXZTCs and those entering the blood. Six metabolites of ZXZTCs were quantitatively determined via high-performance liquid chromatography The hemostatic, analgesic, and anti-inflammatory effects of ZXZTCs were evaluated in various animal models. Results: A total of 36 metabolites of ZXZTCs were identified, including 13 iridoid glycosides, 9 flavonoids, 9 phenylethanol glycosides, 4 phenylpropanoids, and 1 other metabolite. Overall, 11 metabolites of ZXZTCs entered the blood of normal rats. Quantitative analysis of the six main metabolites, shanzhiside methyl ester, chlorogenic acid, 8-O-acetyl shanzhiside methyl ester, forsythin B, luteoloside, and verbascoside, was extensively performed. ZXZTCs exerted hemostatic effects by reducing platelet aggregation and thrombosis and shortening bleeding time. Additionally, ZXZTCs clearly had an analgesic effect, as observed through the prolongation of the latency of writhing, reduction in writhing, and increase in the pain threshold of experimental rats. Furthermore, significant anti-inflammatory effects of ZXZTCs were observed, including a reduction in capillary permeability, the inhibition of foot swelling, and a reduction in the proliferation of granulation tissue. Conclusion: Speculative identification of the overall metabolites of ZXZTCs and those entering the blood can provide a foundation for determining its biologically active constituents. The established method is simple and reproducible and can help improve the quality control level of ZXZTCs as a medicinal product. Evaluating the hemostatic, analgesic, and anti-inflammatory activities of ZXZTCs can help reveal its mechanism.

The Application of Pearls in Traditional Medicine of China and Their Chemical Constituents, Pharmacology, Toxicology, and Clinical Research.

Although pearls are well known by most people, their medicinal value has not been popularized. This article collates the medicinal history of pearls over 2,000 years in China, including the application of pearls in the traditional medicine of China and their various preparations, as well as the progress of their chemical constituents, pharmacology, toxicology, and clinical research. Pearls from three different sources are used as medical materiel by 9 nationalities and 251 prescription preparations in China. In addition, pearls contain various inorganic constituents, such as calcium carbonate, trace elements, and water, and organic constituents, such as amino acids. In terms of pharmacology, pearls have many effects such as calming, improving cognitive ability, being anti-epileptic, promoting bone growth and regeneration, promoting the proliferation and migration of human microvascular endothelial cells, protecting the heart, anti-hemolysis, and anti-oxidation. In terms of toxicology, pearls are safe to take for a long time without exerting obvious adverse reactions. In terms of clinical application, pearls have been used to treat many diseases and conditions, such as convulsions, epilepsy, palpitations, eye diseases, ulcer diseases, skin diseases, or skin lesions. This article provides a reference for the application and research of pearls in the future.

Identification of Hair Growth Promoting Components in the Kernels of Prunus mira Koehne and Their Mechanism of Action.

The application of the seed oil of Prunus mira Koehne (Tibetan name ཁམབུ།), a plant belonging to the Rosaceae family, for the treatment of alopecia has been recorded in Jingzhu Materia Medica (ཤེལ་གོང་ཤེལ་ཕྲེང་།) (the classic of Tibetan medicine) and Dictionary of Chinese Ethnic Medicine. This study aims to reveal the effective components and mechanism of hair growth promotion in the kernel of Prunus mira Koehne. Network pharmacology was used to predict the mechanism of action and effective components in the treatment of the kernel of Prunus mira Koehne. The contents of amygdalin in 12 batches of the kernel of Prunus mira Koehne were determined by HPLC. An animal model of the depilation of KM mice induced by sodium sulfide was created, and five effective components that promoted hair growth were initially screened. In the study of the effectiveness and mechanism of action, KM and C57BL/6 mice are selected as experimental objects, three screening tests for active components of the kernel of P. mira are performed, and three effective components are screened out from the eight components. HE staining was used to detect the number of hair follicles and the thickness of the dermis. RT-PCR and immunohistochemistry were used to evaluate the influence of the expression of indicators in the Wnt/ß-catenin signaling pathway in skin, including ß-catenin, GSK-3ß, and mRNA and protein expression levels of Cyclin D 1 and LEF 1. The network pharmacology study showed 12 signaling pathways involving 25 targets in the treatment of alopecia by the kernel of Prunus mira Koehne. vitamin E (3.125 mg/cm2/d), ß-sitosterol (0.061 mg/cm2/d), and linoleic acid (0.156 mg/cm2/d) in the kernel of Prunus mira Koehne can promote hair growth in mice, and the mechanism of action may be related to the Wnt/ß-catenin pathway.

Progress in ICP-MS Analysis of Minerals and Heavy Metals in Traditional Medicine.

Aim: This study systematically reviewed the application of ICP-MS and its combined technology in the determination of mineral and heavy metal elements in medicinal materials derived from plants, animals, minerals and their preparations (Chinese patent medicine), and biological products. It provides a reference for improving the quality standard of traditional medicine and exploring the effective components, toxic components, and action mechanism of traditional medicine. Materials and Methods: A total of 234 articles related to the determination of mineral and heavy metal elements in medicinal materials derived from plants, animals, and minerals and their preparations (Chinese patent medicine) were collected from PubMed, CNKI, Web of Science, VIP, and other databases. They were classified and sorted by the inductively coupled plasma-mass-spectrometry (ICP-MS) method. Results: Of the 234 articles, 154 were about medicinal materials derived from plants, 15 about medicinal materials derived from animals, 9 about medicinal materials derived from minerals, 46 about Chinese patent medicine, 10 about combined technology application, and 3 about drugs being tested after entering the body. From the 154 articles on medicinal materials derived from plants, 76 elements, including Cu, Cd, Pb, As, Cr, Mn, and Hg, were determined, of which the determination of Cu was the most, with 129 articles. Medicinal materials derived from the roots, stems, leaves, flowers, and fruits and seeds of plants accounted for 25.97%, 18.18%, 7.14%, 7.79%, and 14.94%, respectively. Moreover, medicinal materials derived from the whole plants accounted for 14.94%, and other medicinal materials derived from plants and soil accounted for 11.04%. A total of 137 of the tested medicinal materials were from traditional Chinese medicine, accounting for 88.96%, 12 were from Arabic medicine (including Unani), accounting for 7.79%, 2 were from Tibetan medicine of China, and 1 was from Mongolian medicine of China, 1 was from Miao medicine of China, and 1 was from Zhuang medicine of China. In the 15 articles on medicinal materials derived from animals, 49 elements such as Cu, As, Cd, Hg, Se, Pb, and Mn were determined, of which Cu was the most. All the tested medicinal materials belong to traditional Chinese medicine. From the nine articles on medicinal materials derived from minerals, 70 elements such as Fe, Cu, Zn, Al, As, Se, and Na were determined, of which Fe, Cu, and Zn were the most. The tested medicinal materials all belong to traditional Chinese medicine. From the 46 articles on Chinese patent medicine, 62 elements such as Cu, As, Pb, Cd, Hg, Ni, and Cr were determined, of which Cu was the most. Regarding the tested Chinese patent medicine, 38 articles belong to traditional Chinese medicine, 6 to Tibetan medicine, and 2 to Mongolian medicine of China. Three articles determine the content of metal elements in biological samples such as animal hepatic venous blood, abdominal aortic blood, brain, liver, kidney, urine, and feces, and one article determines the content of metal elements in human lung and serum. From the 10 articles combined with liquid chromatography and gas chromatography, 16 elements such as MMA, DMA, AsIII, AsV, AsB, AsC, and AsI3 were determined, of which MMA and DMA were the most. It can realize elemental morphology and isotope analysis. The tested medicinal materials and Chinese patent medicine belong to traditional Chinese medicine. Conclusion: ICP-MS was applied the most in traditional Chinese medicine, followed by Arabic medicine. ICP-MS was used to determine more medicinal materials derived from plants, and Cu was determined the most. The characteristic inorganic element spectrum of medicinal materials can also be established. ICP-MS and its combined technology are widely used in Chinese patent medicine, but the test of biological samples is the least. The information provided in this article can provide a reference for improving the quality standard of traditional medicines and exploring the active ingredients and toxic ingredients and their mechanism of action.

Prunus mira Koehne in Sichuan, China: Recorded History as a Medicine and Food, Modern Applications, Distribution, and Ethnobotanical Investigations.

Prunus mira Koehne, a Prunus plant in the Rosaceae family, is named ཁམབུ། in Tibetan and "Guang he tao" in Chinese. It is mainly distributed in Tibet Autonomous Region, Yunnan Province, and Sichuan Province in China. It is also a rare "living fossil group" of peach genetic resources in the world. It is used in traditional Chinese medicine for the treatment of dysmenorrhea, injury, intestinal dryness, constipation, and other diseases, and is used in Tibetan medicine for the treatment of hair, eyebrows, and beard shedding. In this article, the botanical characteristics, medicinal history, modern applied research, and ethnobotanical investigation of P. mira were recorded and evaluated. P. mira was first recorded in Dumu Materia Medica. P. mira in Sichuan Province is mainly distributed in Ganzi Tibetan Autonomous Prefecture, and has certain economic and medicinal value. P. mira has high nutritional composition. It is made into high-quality edible oil, cosmetic base oil, fruit juice, fruit wine, fruit vinegar, "Liang guo", and other products. Oleic acid and linoleic acid are the main fat-soluble components of P. mira, which has an anti-inflammatory medicinal value and promotes hair growth. Its longevity and cold resistance can bring great genetic value and play an important role in maintaining peach genetic diversity. At present, there are few studies on the pharmacological effects of specific active components of P. mira and there are also few clinical studies. We can continue to study these aspects in the future. At the same time, products of P. mira have great market potential. All in all, P. mira is very worthy of further research and development.

Traditional Indian medicine in China: The status quo of recognition, development and research.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Indian medicine is one of the oldest medical systems and remains popular worldwide. Traditional medicine systems in China and India have historical origins pertaining to mutual learning, reference, and development from medical theory to the drugs used. The exchange of traditional medicine between China and India began in the Qin and Han Dynasties (221 BC-220 AD), prospered in the Tang Dynasty (618-907 AD), and declined after the Song Dynasty (960-1279 AD). It was also directly related to the rise and fall of Buddhism. The traditional medicines of the two countries are highly complementary because of differences in geographical climate and the modernisation process of traditional medicine. AIM: This review aimed to understand the spread and development of traditional Indian medicine in China to further promote exchange and cooperation between China and India in the field of traditional medicine. MATERIALS AND METHODS: We performed a systematic search of MEDLINE via PubMed, CNKI, Science Direct, Sci-Hub, and other databases using the terms 'traditional Indian medicine' or 'Indian medicine' or 'Ayurveda' or 'Yoga' or 'Unani', and limiting the search to articles published between 1958 and 2019. We analysed the sources, publication date, type, and topic of the retrieved articles/studies. RESULTS: Based on the results of research on traditional Indian medicine carried out by Chinese scholars, 518 academic papers and 60 classic works published in China and abroad were collected. The results showed the following. First, Chinese scholars have systematically investigated traditional Indian medicine including its composition, management, and education; the scale of medicinal and pharmaceutical plants; protective measures of intellectual property rights of traditional medicine; and international promotion of Yoga. Second, studies have examined the development status of traditional Indian medicine in China including the spread of Yoga in the country and the industrial scale of, education in, existing problems in, and clinical research on Yoga. In addition, Chinese scholars conducted research on and the translation of classic works and terms of Ayurveda, and studied the theory, treatment, and medicine thereof. Third, the historical exchange and trading status of traditional medicine between India and China have been discussed, including the exchange of traditional medicine between the two countries, effect of traditional Indian medicine on Chinese Buddhism, and minority medicine and trade in medicinal materials between the two countries. CONCLUSION: India attaches great importance to the management of, education in, and industry of traditional medicine, and has made various efforts to protect intellectual property rights. Indian Yoga is very popular in China, and Chinese scholars have conducted some clinical research thereon. However, regulatory systems and legislation for Yoga are lacking in China. At present, traditional Chinese medicine scholars have an enhanced understanding of the term Yoga and less knowledge of the terms Ayurveda, Siddha, Unani, and similar concepts. We suggest that Chinese scholars further study the classic works, basic theories, treatment of clinical diseases, medicinal materials, and prescriptions compounding traditional Indian medicine. The results of this study highlight directions for Chinese scholars to pursue in further studying traditional Indian medicine comprehensively, and will help promote exchange and cooperation between China and India in the field of traditional medicine.

Birth month is associated with learning capacity in childhood in Northeast China.

It is difficult to evaluate long-term ventilation and indoor-outdoor temperature variation on-site in the birth residence so as to investigate their associations with learning capacity from childhood through adolescence. Here, we conducted a questionnaire-based retrospective cohort study in ten schools from two northeast China cities with warm summers and severe cold winters when residences had very low air exchange rates. Scores for Chinese, Mathematics, and English in the final exams of the summer semester in June 2018 were collected to evaluate learning capacity. We surveyed 6238 students aged 14.7 (SD: 2.1) years old. Using the 2nd quarter (April-May-June) birth as reference, 4th quarter (October-November-December) birth consistently was significantly associated with lower scores in Chinese in bivariate (ß, 95%CI: -3.2, -4.3 to -2.0) and multivariate (-1.8, -2.4 to -0.8) linear regression analyses. Stratified sub-analyses showed significant associations for male (-2.4, -3.7 to -1.1), urban (-2.4, -3.4 to -1.4), and primary students (-2.9, -4.5 to -1.4). Since household ventilation and indoor-outdoor temperature variation had great differences between the 2nd and 4th quarter of year, our results suggest that these two factors in the birth residence could be associated with learning capacity in childhood, especially for male and primary students in northeast China.