Drug–drug interactions of silymarin on the perspective of pharmacokinetics

Silymarin, which is extracted from the milk thistle (Silybum marianum), has been used for centuries for treating hepatic disorders and its hepatoprotective effects have been known for hundreds of years. Silymarin is a mixture of polyphenoic flavonoids, which include silibinin (silybin A and silybin B), isosilyin A and B, silychristin A and B, silydianin and other phenol compounds. The pharmacokinetics of silibinin shows fast absorption and elimination. Silymarin undergoes phase I and phase II metabolism, especially phase II conjugation reactions, it undergoes multiple conjugation reactions, and is primarily excreted into bile and urine. Silymarin has a good safety profile, but little is known regarding its potential for drug interaction. Silymarin has limited effect on the pharmacokinetics of several drugs in vivo; despite silymarin decreasing the activity of cytochrome P-450 (CYPs) enzymes, UDP-glucuronosyltransferase (UGT) enzyme, and reducing P-glycoprotein (P-gp) transport. Health-care practitioners should caution patients against co-administration of silymarin and pharmaceutical drugs.     

Antinociceptive activities of the methanol extract of the bulbs of Dioscorea bulbifera L. var sativa in mice is dependent of NO–cGMP–ATP-sensitive-K channel activation

Ethnopharmacological relevance

Dioscorea bulbifera var sativa is a medicinal plant commonly used in Cameroonian traditional medicine to treat pain and inflammation.

Aim

The present work evaluated the effects of the methanol extract of the bulbs of Dioscorea bulbifera in inflammatory and neuropathic models of pain and further investigated its possible mechanism of action.

Materials and methods

The effects of Dioscorea bulbifera administered orally at the doses of 250 and 500 mg/kg were tested in mechanical hypernociception induced by intraplantar (i.pl.) injection of complete Freund's adjuvant (CFA), lipopolysaccharides (LPS) or prostaglandin-E₂ (PGE₂), as well as in partial ligation sciatic nerve (PLSN), nociception induced by capsaicin and thermal hyperalgesia induced by i.pl. injection of CFA. The therapeutic effects of Dioscorea bulbifera on PGE₂-induced hyperalgesia were evaluated in the absence and in the presence of l-NAME, an inhibitor of nitric oxide synthase (NOS) and glibenclamide, an inhibitor of ATP-sensitive potassium channels.

Results

The extract showed significant antinociceptive effects in persistent pain induced by CFA and on neuropathic pain induced by PLSN. The effects of Dioscorea bulbifera persisted for 5 days after two administrations in CFA-induced hypernociception. Dioscorea bulbifera significantly inhibited acute LPS-induced pain but failed to reduce thermal hypernociception and capsaicin-induced spontaneous nociception. The antinociceptive effects of this plant extract in PGE₂ model was antagonized by either l-NAME or glibenclamide.

Conclusion

Present demonstrate the antinociceptive activities of Dioscorea bulbifera both in inflammatory and neuropathic models of pain and these effects may result, at least partially, from its ability to activate the NO–cGMP–ATP-sensitive potassium channels pathway.     

Chemical profile of the active fraction of Yi-Gan San by HPLC–DAD–Q-TOF–MS and its neuroprotective effect against glutamate-induced cytotoxicity

Yi-Gan San（YGS）, a traditional Chinese medicine for dementia-related symptoms, was previously fractionated. One active fraction, YGS40 exhibited a neuroprotective effect against glutamate-induced cytotoxicity. In the present study, high-performance liquid chromatography, coupled with diode-array detection and quadrupole time-of-flight mass spectrometry, was applied for the identification of its chemical constituents and for quantification studies. The chemical profile of YGS40 consisted of sixty-four identified or tentatively characterized compounds. The levels of the major marker compounds increased significantly in the mixed decoction compared with those in the single plant decoction. The results suggest the high precision of the analyses of most of the constituents in YGS40 and establish the quantitative variations of the major marker compounds between the single and mixed decoction processes.     

Is the yin–yang nature of Chinese herbal medicine equivalent to antioxidation–oxidation?

It has been suggested that yin-yang theory described in traditional Chinese medicine is somewhat equivalent to the modern theory of antioxidant-oxidant balance. Some yin-tonic Chinese herbal medicines possess antioxidant properties. In this context, the DNA protective effect of 12 yin-tonic and 13 yang-tonic herbs were tested using the single cell gel electrophoresis (comet) assay. Lymphocytes from three healthy subjects were pre-incubated with aqueous herb extract, and the comet assay was performed on treated, untreated, challenged and unchallenged cells in parallel, oxidant challenge being induced by 5 min exposure to hydrogen peroxide. Results using this ex vivo cellular assay showed protection by some herbs. Seven out of 12 yin-tonic Chinese herbs demonstrated decreased DNA damage after treatment while 10 out of 13 yang-tonic herbs showed protection. Among 25 herbs tested, rhizome of Ligusticum sinensis Oliv. and aerial part of Artemisia annua L. demonstrated greatest DNA protective effect. Results indicated that the yin nature of herbs may not be necessarily associated with superior antioxidative effect to yang-tonic herbs, at least in terms of DNA protection against oxidant challenge.     

The mechanism of the opening of the blood–brain barrier by borneol: A pharmacodynamics and pharmacokinetics combination study

Ethnopharmacological relevance

Borneol is widely used in traditional Chinese medicine to facilitate the distribution of central nervous system (CNS) drugs in brain due to its ability to open blood–brain barrier (BBB), however, the underlying mechanism is still unclear. In this study, the effect of borneol on different brain regions were investigated to explore the mechanism.

Materials and methods

After oral administration of borneol (0.1, 0.2 g/kg) for seven consecutive days, SD rats were injected with Rh123 (1.0 mg/kg). The concentrations of Rh123 were detected in four brain regions of cortex, hippocampus, hypothalamus and striatum by a small animal vivo imaging system and a fluorescence microplate reader respectively. The ultrastructures of BBB were examined. Moreover, the expressions of the four transporters of ATP-binding cassette (ABC) family, multidrug resistance 1a (Mdr1a), multidrug resistance 1b (Mdr1b), multidrug resistance protein 1 (Mrp1), Mrp4, Mrp5 and breast cancer resistance protein (Bcrp) in the four brain regions were analyzed. Finally, the deliveries of borneol in the plasma and the four brain regions were examined by a pharmacokinetics study.

Results

Administration of 0.2 g/kg borneol produced loose structure in the tight junction and void structure between the endothelial cell and mesangial cell. Borneol at 0.1 g/kg and 0.2 g/kg increased the delivery of Rh123 in hippocampus and hypothalamus obviously. Permeability index followed a similar trend. Protein expression assays showed that borneol decreased the expression of Mdr1 and Mrp1 in hippocampus and hypothalamus. Further RT-PCR study showed that borneol decreased the expressions of both Mdr1a and Mdr1b in hippocampus and hypothalamus. The pharmacokinetics study demonstrated that the delivery of borneol in cortex was the most and that in striatum the least, with the deliveries of borneol in hippocampus and hypothalamus in between.

Conclusions

Borneol showed tissue specific BBB-opening effect, which was associated with its regulation of the ultrastructure of brain tissues and the expressions of Mdr1a, Mdr1b and Mrp1. The present study indicated that borneol should be used in concert with drugs targeting hippocampus or hypothalamus to exert its synergistic effect to the maximum.     

Investigation of the Test–Retest Reliability and Inter-Rater Agreement of Traditional Chinese Medicine-Based Pulse Practitioners

Objective: The objective of this study was to assess the test–retest reliability and inter-rater agreement between the traditional Chinese medicine(TCM) pulse diagnosis between two Indian TCM practitioners. Methods: A total of 300 participants were evaluated for their bilateral pulse based on TCM independently by two investigators with similar years of experience but who graduated from different medical schools.The investigators who were blinded diagnosed the participants as per TCM based on the...     

H NMR-based metabonomic analysis of the effect of optimized rhubarb aglycone on the plasma and urine metabolic fingerprints of focal cerebral ischemia–reperfusion rats

Ethnopharmacological relevance

The ischemia cerebrovascular disease is one of leading causes of death and long-term disability in modern society. Rhubarb is one of the common traditional Chinese medicine with many effects, and the main pharmacodynamic ingredients are aloe-emodin, rhein, emodin, chrysophanol and physcion. The five components are also known as rhubarb aglycone. Rhubarb aglycone has been confirmed to play a remarkable curative effect on cerebral ischemia, but the mechanism is not clear. In this study, ¹H NMR-based metabonomics approach has been used to investigate the protective effect of the optimized rhubarb aglycone on rats of cerebral ischemia–reperfusion.

Materials and methods

Male Wistar rats were divided into four groups: sham operation group, model group, Nimodipine group and the optimized rhubarb aglycone group. Based on ¹H-NMR spectra of plasma and urine, principal component analyses were performed to identify different metabolic markers and explore the changes of associated biochemical pathways. Behavior research and brain histopathology examinations were also performed.

Results

It was showed that the optimized rhubarb aglycone treatment improved neurological deficits, cerebral infarction and neuronal apoptosis. Principal component analysis scores plots demonstrated that the cluster of model rats was separated from those of sham operation group; rats of the optimized rhubarb aglycone group were classified from model group, but the optimized rhubarb aglycone group closed to the sham operation group. Optimized rhubarb aglycone regulated the associated amino acid, energy and lipid metabolisms disturbed in model rats.

Conclusion

Our results suggested that the optimized rhubarb aglycone had protective effect on rats of cerebral ischemia–reperfusion and explored the metabolic regulation mechanism. This work showed that the NMR-based metabonomics approach might be a promising approach to study mechanisms of traditional Chinese medicines.     

Traditional uses of medicinal plants against malarial disease by the tribal communities of Lesser Himalayas–Pakistan

Ethnopharmacological relevance

Malaria is among the most prevalent infectious diseases in the developing countries of world. Estimated number of annual malaria episodes in Pakistan is 1.5 million, but very little is known about medicinal plant species of Pakistan, which have great potential against malarial disease. Present study was aimed to document medicinal plant species used by the local inhabitants of Lesser Himalayas–Pakistan to treat malaria.

Materials and methods

Data were collected through interviews, questionnaires and contributor observation. A total of 55 informants aged between 25 and 80 years who were familiar with malarial disease participated in the survey.

Results

A total of 84 plant species belonging to 69 genera and 50 families were recorded to treat malaria. Asteraceae was found as most cited botanical family with (11.9%) representation, followed by Lamiaceae (5.9%), Solanaceae and Verbenaceae (4.7%) and Violaceae (3.5%) respectively. About 60% of the inhabitants prefer herbal treatment by local herbalists or self-treatment with locally available medicinal plant species. Of the plants identified during present investigation against malaria, Azadirachta indica, Swertia chirayita and Swertia ciliata exhibited uppermost frequency of encounter (36.3%) and corresponding PR value 5. About 67.2% of the botanical taxa are reported for the first time in the treatment of malaria. It was observed thatover harvesting is the foremost threat to medicinal plant species of the study area.

Conclusion

Present survey indicates that traditional knowledge about the use of plant species against various diseases and particularly to treat malaria is in decline. Similarly anthropogenic pressure, over exploitation and grazing of the botanical taxa are the major concerns regarding medicinal plant biodiversity loss. Frequently utilized plant species with significant malarial reduction should be authenticated by in vitro and in vivo standard tests     

Scientific connotation of “treating different diseases with the same method” from the perspective of metabolic–immune dysregulation in inflammation-mediated carcinogenesis of digestive organs

Inflammation-mediated carcinogenesis develops in the context of chronic inflammation and is a significant cause of cancer within the digestive system. In the chronic inflammation microenvironment, the metabolic activity of tissue cells undergoes extensive changes, which interfere with the normal function of immune cells. Dysregulation of cell metabolism and immune function has been identified as a key factor contributing to inflammation-mediated carcinogenesis within the major digestive organs, such as the stomach, liver, and colorectum. This metabolic–immune imbalance also corresponds to traditional Chinese medicine (TCM) theories of “yin-yang disharmony” and “disharmony between Ying-nutrients and Wei-defense.” The metabolic–immune imbalance has also been regarded as the key factor supporting “treatment of different diseases with the same method,” in which the same approach is adopted in the treatment of different conditions. In the TCM treatment process, it is necessary to first identify TCM patterns and then apply the corresponding TCM to correct the dysregulated metabolic and immune function, thereby blocking the progression from inflammation to malignancy. Our study findings deepen the TCM understanding of metabolic–immune dysregulation and the relationship between metabolic–immune dysregulation, pattern identification, and treatment method. They also provide new insights for the treatment of inflammation-mediated carcinogenesis in major digestive organs and help us further explore the scientific connotation of the TCM strategy of “treating different diseases with the same method.     

A review of the literature on randomized controlled trials of acupuncture and moxibustion in the treatment of chronic prostatitis/chronic pelvic-pain syndrome within 2016–2021

Chronic prostatitis (CP)/chronic pelvic-pain syndrome (CPPS) is a common urinary-system disease with a high incidence in young and middle-aged men, seriously affecting patients’ ability to work and their quality of life (QoL). Western medicine (WM) has some limitations in treating CP/CPPS. Acupuncture is an ancient Chinese medical method that is commonly used to treat this condition and has a relatively good effect on it. Many randomized controlled trials (RCTs) on this subject have been published. For this study, we searched the China National Knowledge Infrastructure (CNKI), Chinese Science and Technology Periodical (VIP), Wanfang, SinoMed, and PubMed databases for RCTs on acupuncture treatment of CP/CPPS in the last 5 years (2016/01/01–2021/12/01). In addition, we conducted analysis and research, aiming to summarize acupuncture treatment in CP/CPPS RCTs and the clinical efficacy, with the goal of providing clinical reference. A total of 466 related documents were retrieved in the search, and 62 articles were retained after screening. We obtained RCT information on acupuncture treatment of CP/CPPS. The results showed that several relevant clinical studies have been performed over the last 5 years and that acupuncture and moxibustion have better curative effect on CP/CPPS than WM. Due to the small number of included studies, more experimental evidence is needed to verify the clinical efficacy of acupuncture.     

Summary of the 1~(st) Group Meeting on the Who Standard of the Location of Acupoints

On February 22 ~25 ,2005 ,the 1stgroup meeting onformulating WHOstandard of thelocation of acupuncture points was held in Oriental Culture Hotel ,Beijing ,China .Five expertsfrom Republic of Korea ,Japan and China attendedthis meeting .They were Prof . Ki m Yong-Suk (Korea) ,Prof . Shuichi Katai (Japan) , Prof . Wang Xuetai (China) , Prof . Huang Longxiang (China) and Prof .Jin Zhigao (China) . Dr Choi Seung-Hoon ,the convener of this meeting ,fromthe Western Pacific Region of …     

Announcement of Compiling the Special Issue of Acupuncture in the Whole World-Global Events Record of Acu-Moxi

Commemorate the 20th Anniversary of the Foundation of World Federation of Acupuncture-Moxibustion Societies (WFAS)     

WFAS representatives attended the 120^th session of the Executive Board of WHO

The 120th session of the Executive Board of WHO was held between 22nd and 30th, January, 2007, in Geneva, the headquarters of WHO.     

Study of the Effect of Acupuncture on the Total Acidity of Gastric Juice and Pepsin＇s Activity

To know the effect of the total acidity of gastric juice and pepsin‘s activity. Methocls:By observing the effect on gastric mucosa through puncturing and moxibusting the acupuncture points of Zusanli (ST 36), Zhongwan (CV 12), Tianshu (ST 25) chronic shrinking gastritics in rat model. Results: We found acupuncture can cut down the quantity of emission of the total acidity of gastric juice effectively,decrease the activity of pepsin, remove superoxygen negative ion effectively, reduce the damage to the organism and increase the activity of SOD. Conclusions: The study showed that the activity can play a role in protecting the gastric mucosa.     

Mechanism of the Reversal Effect of Acupuncture on the Fall of Blood Pressure Induced by Angiotensin-（1-7） in the Caudal Ventrolateral Medulla of Rats

目的：研究电针逆转血管紧张素-（17）[Ang-（1—7）]在大鼠延髓尾端腹外侧区（CVLM）引起血压降低的作用机制。方法：采用中枢核团微量注射和微透析，以及高效液相色谱（HPLC）荧光检测等技术观察Ang（17）及其选择性受体拮抗剂（D-Ala7）-Ang-（1—7）（Ang-779）在大鼠CVLM引起血压改变时氨基酸类神经递质释放的变化以及电针对血压和氨基酸类递质释放的影响。结果：在CVLM微量注射Ang（1—7）可引起血压降低，同时伴该区内兴奋性氨基酸谷氨酸（Glu）释放增多和抑制性氨基酸牛磺酸（Trau）释放减少；相反，在CVLM微量注射Ang779则可引起血压升高，同时伴Glu释放减少和Tau释放增多。在相当于人”足三里”穴位电针20min，可分别抑制在CVLM微量注射Ang—（1-7）或Ang779所引起的血压降低或升高，同时也能部分抵消注射Ang-（17）或Ang779所引起的Glu、Tau释放的改变。结论：电针逆转Ang（1-7）或Ang-779在CVLM引起的降压或升压作用可能与Glu、Tau释放量的改变有关。     

Effects of Banxiaxiexin Decoction on the SCF Gene Expression in the Stomach Wall of Rat Model of Electrogastric Dysrhythmias

Electrogastricdysrhythmiasiscommoninclinicandrelatedtogastrointestinaltractfunctionaldiseases .Itisoneoftheim portantreasonsingastrointestinaltractmotordisorders.RecentstudiesshowthattheinterstitialcellsofCajal (ICC)adjustthemotorofgastrointestinaltract.ThenumberandstructureofICCinpartofthegastrointestinaltracthavechangedinsomemotivitydiseasessuchascardioinchalasia ,diabeticgastroparesis,etc .TheICCsexpressc -kitgene .TheirdevelopmentandthephenotypelastingaredependonthesignalofKitandthepr…