Interacciones potenciales entre productos herbolarios con fármacos hipoglucemiantes en adultos mayores con diabetes mellitus, en una zona rural mexicana / Potenciais interacções entre produtos à base de plantas e medicamentos hipoglicemiantes em adultos mais velhos com diabetes mellitus no Mexico rural / Potential interactions between herbal products with hypoglycemic drugs in older adults with diabetes mellitus in rural Mexico

Introducción: El 50% de la población mundial usa tratamientos alternativos como productos herbarios. El 20% los consume de manera simultánea con algún tratamiento farmacológico para el control la Diabetes Mellitus tipo 2; enfermedad prevalente en adultos mayores. Es escasa la información acerca de las interacciones medicamentosas que pudieran producirse, siendo responsables de más de 7,000 muertes al año. Objetivo: Identificar los productos herbarios de mayor consumo del Adulto Mayor con Diabetes Mellitus Tipo 2, en Chapulco, Puebla, México y describir las posibles interacciones medicamentosas entre fármaco hipoglucemiante ­ producto herbario reportados en la literatura científica. Metodología: Estudio observacional, prolectivo, transversal, descriptivo, en una población de 35 adultos mayores diabéticos, con edad promedio de 70±7 años. Para la identificación de los productos herbarios de uso común y sus aplicaciones terapéuticas se aplicó el cuestionario U-PLANMED. Resultados: Se identificaron 50 productos herbarios y 18 combinaciones entre estos a la vez. El 40% de los participantes consumen simultáneamente más de dos productos herbarios con uno o dos fármacos hipoglucemiantes. Entre los productos de mayor consumo se encuentran el nopal (Opuntia ficus-indica L.), la manzanilla (Matricaria chamomilla L.) y el zacate de limón (Cymbopogon citratus DC. Stapf.). Las interacciones medicamentosas potenciales identificadas, principalmente en estudios experimentales en animales, sugieren que, existe una acción hipoglucemiante del producto herbario al aumentar la capacidad orgánica sobre la secreción/liberación de insulina endógena. Conclusiones: Se ha evidenciado la presencia de interacciones medicamentosas ante el consumo simultaneo de fármacos prescritos para el control de la diabetes mellitus tipo 2 con productos herbarios. Es necesario que, los profesionales en atención a la salud identifiquen el uso de dichos productos y orienten a los adultos mayores sobre las posibles repercusiones en los niveles de glucosa ante el consumo.

Introduction: 50% of the world's population uses alternative treatments such as herbal products. Twenty percent use them in conjunction with some form of pharmacological treatment to control type 2 diabetes mellitus, a disease prevalent in older adults. There is little information on the drug interactions that may occur, which are responsible for more than 7,000 deaths per year. Objective: To identify the most consumed herbal products among older adults with type 2 diabetes mellitus in Chapulco, Puebla, Mexico, and to describe the possible drug-drug interactions between hypoglycemic drugs and herbal products reported in the scientific literature. Methodology: Observational, prospective, cross-sectional, descriptive study in a population of 35 diabetic older adults with a mean age of 70±7 years. The U-PLANMED questionnaire was used to identify commonly used herbal products and their therapeutic applications. Results: Fifty herbal products and 18 combinations of them were identified. Forty percent of the participants used more than two herbal products simultaneously with one or two hypoglycemic drugs. The most used products included prickly pear cactus (Opuntia ficus-indica L.), chamomile (Matricaria chamomilla L.), and lemon grass (Cymbopogon citratus DC. Stapf.). Potential drug-drug interactions identified mainly in experimental animal studies suggest that there is a hypoglycemic effect of the herbal product by increasing the organic capacity on endogenous insulin secretion/release. Conclusions: The presence of drug-drug interactions has been demonstrated with the simultaneous consumption of drugs prescribed for the control of type 2 diabetes mellitus with herbal products. It is necessary for health care professionals to recognize the use of such products and to inform older adults about the possible repercussions on glucose levels when consuming them.

Introdução: 50% da população mundial utiliza tratamentos alternativos como os produtos à base de plantas. Vinte por cento utilizam-nos em conjunto com algum tipo de tratamento farmacológico para controlar a diabetes mellitus tipo 2, uma doença prevalente em adultos mais velhos. Há pouca informação sobre as interacções medicamentosas que podem ocorrer e que são responsáveis por mais de 7.000 mortes por ano. Objetivos: Identificar os produtos fitoterápicos mais consumidos entre os idosos com diabetes mellitus tipo 2 em Chapulco, Puebla, México, e descrever as possíveis interações medicamentosas entre medicamentos hipoglicemiantes e produtos fitoterápicos relatados na literatura científica. Metodologia: Estudo observacional, prospetivo, transversal e descritivo numa população de 35 idosos diabéticos com uma idade média de 70±7 anos. O questionário U-PLANMED foi utilizado para identificar os produtos fitoterápicos mais utilizados e suas aplicações terapêuticas. Resultados: Foram identificados 50 produtos à base de plantas e 18 combinações dos mesmos. Quarenta por cento dos participantes utilizaram mais de dois produtos à base de plantas em simultâneo com um ou dois medicamentos hipoglicemiantes. Os produtos mais utilizados foram o cato de figo da Índia (Opuntia ficus-indica L.), a camomila (Matricaria chamomilla L.) e o capim-limão (Cymbopogon citratus DC. Stapf.). As potenciais interacções medicamentosas identificadas principalmente em estudos experimentais em animais sugerem que existe um efeito hipoglicémico do produto à base de plantas através do aumento da capacidade orgânica na secreção/libertação de insulina endógena. Conclusões: A presença de interacções medicamentosas foi demonstrada com o consumo simultâneo de medicamentos prescritos para o controlo da diabetes mellitus tipo 2 com produtos à base de plantas. É necessário que os profissionais de saúde reconheçam o uso de tais produtos e informem os idosos sobre as possíveis repercussões nos níveis de glicose ao consumi-los.

Sorting and Elaborating on the Combination Theory of Herb Pairs / 中医杂志

As the smallest combination unit of Chinese medicinals， herbal pairs serve as the bridge between medicinals and formulas， whose combination theory reflects the basic characteristics of Chinese medicinals combination and the core essence of prescription composition. Simultaneously， as a key combination of medicinals in clinical treatment of diseases， syndromes， and symptoms， herbal pairs are the main form of clinical medication in traditional Chinese medicine （TCM） as well as the characteristic advantage of treating diseases. This article summarized that “mutual complement of medicinals of same or antagonism flavor and nature” theory is the theoretical origin， and efficacy-enhancement and toxicity-attenuation is the core purpose of the combination of herbal pairs. The property theory of Chinese medicinals and the thought of differentiation and treatment are the main basis of the combination of herbal pairs， and pertinence and flexibility are the key points in clinical application. All mentioned above are expected to provide theoretical guidance for the clinical use and modern research of herbal pairs.

Ephedra Herb extract ameliorates adriamycin-induced nephrotic syndrome in rats via the CAMKK2/AMPK/mTOR signaling pathway / 中国天然药物

This study aimed to investigate the effect and mechanisms of Ephedra Herb (EH) extract on adriamycin-induced nephrotic syndrome (NS), providing an experimental basis for the clinical treatment of NS. Hematoxylin and eosin staining, creatinine, urea nitrogen, and kidn injury molecule-1 were used to evaluate the activities of EH extract on renal function. The levels of inflammatory factors and oxidative stress were detected by kits. The levels of reactive oxygen species, immune cells, and apoptosis were measured by flow cytometry. A network pharmacological approach was used to predict the potential targets and mechanisms of EH extract in the treatment of NS. The protein levels of apoptosis-related proteins and CAMKK2, p-CAMKK2, AMPK, p-AMPK, mTOR and p-mTOR in the kidneys were detected by Western blot. The effective material basis of EH extract was screened by MTT assay. The AMPK pathway inhibitor (compound C, CC) was added to investigate the effect of the potent material basis on adriamycin-induced cell injury. EH extract significantly improved renal injury and relieve inflammation, oxidative stress, and apoptosis in rats. Network pharmacology and Western blot results showed that the effect of EH extract on NS may be associated with the CAMKK2/AMPK/mTOR signaling pathway. Moreover, methylephedrine significantly ameliorated adriamycin-induced NRK-52e cell injury. Methylephedrine also significantly improved the phosphorylation of AMPK and mTOR, which were blocked by CC. In sum, EH extract may ameliorate renal injury via the CAMKK2/AMPK/mTOR signaling pathway. Moreover, methylephedrine may be one of the material bases of EH extract.

Reduced SARS-CoV-2 infection risk is associated with the use of Seven-Flavor Herb Tea: A multi-center observational study in Shanghai, China / 中西医结合学报

OBJECTIVE@#Omicron, a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant, is responsible for numerous infections in China. This study investigates the association between the use of Seven-Flavor Herb Tea (SFHT) and the risk of SARS-CoV-2 infection to develop precise and differentiated strategies for control of the coronavirus disease 2019 (COVID-19).@*METHODS@#This case-control study was conducted at shelter hospitals and quarantine hotels in China. A total of 5348 laboratory-confirmed COVID-19 patients were enrolled between April 1 and May 31, 2022, while 2190 uninfected individuals served as healthy controls. Structured questionnaires were used to collect data on demographics, underlying diseases, vaccination status, and use of SFHT. Patients were propensity-score-matched using 1:1 nearest-neighbor matching of the logit of the propensity score. Subsequently, a conditional logistic regression model was used for data analysis.@*RESULTS@#Overall, 7538 eligible subjects were recruited, with an average age of [45.54 ± 16.94] years. The age of COVID-19 patients was significantly higher than that of uninfected individuals ([48.25 ± 17.48] years vs [38.92 ± 13.41] years; t = 22.437, P < 0.001). A total of 2190 COVID-19 cases were matched with uninfected individuals at a 1:1 ratio. The use of SFHT (odds ratio = 0.753, 95% confidence interval: 0.692, 0.820) was associated with a lower risk of SARS-CoV-2 infection compared to untreated individuals.@*CONCLUSION@#Our findings suggest that taking SFHT reduces the risk of SARS-CoV-2 infection. This is a useful study in the larger picture of COVID-19 management, but data from large-sample multi-center, randomized clinical trial are warranted to confirm the finding. Please cite this article as: Zhang SX, Chen XX, Zheng Y, Cai BH, Shi W, Ru M, Li H, Zhang DD, Tian Y, Chen YL. Reduced SARS-CoV-2 infection risk is associated with the use of Seven-Flavor Herb Tea: A multi-center observational study in Shanghai, China. J Integr Med. 2023; 21(4):369-376.

Indian Traditional Treatments for Psoriasis: A Critical Appraisal of Available Evidence Supporting Efficacy / 中国结合医学杂志

OBJECTIVE@#To examine data from studies supporting the clinical efficacy of medical approaches from India traditional systems of medicines like Ayurveda, Unani, Siddha, and Homeopathy for psoriasis using outcome indicators employed in clinical practice and research.@*METHODS@#Searches were conducted between December 2019 and September 2020 in databases PubMed, Scopus, Web of Science and Ovid Medline using search terms including traditional, complementary, psoriasis, Kushtha, Ayurveda, Siddha, Unani, Homeopathy and clinical. Controlled trials, case series and case reports published from India were included.@*RESULTS@#Data of 17 selected studies were extracted. Treatment efficacy in terms of improvement in Psoriasis Area and Severity Index (PASI) score or/and percentage reduction in score (PASI 50, PASI 75 and PASI 90) or/and patient-reported outcomes using instruments like Dermatology Life Quality Index and Psoriasis Disability Index were noted. All studies reported good improvement as per the study specific outcome. However, study characteristics, including study design, sample size, follow-up period, inclusion and exclusion criteria were heterogeneous, and the choice of outcome measures was not adequate to conclude the effectiveness of intervention. The use of some herbs as common ingredients in several formulations across different systems of medicines were noted in analyzing individual formulation.@*CONCLUSIONS@#Future studies must incorporate a comprehensive study design with specific outcome measures like PASI, PASI 75, PASI 90, quality of life parameters, compliance to medications, adverse reactions, remission period, relapse rate and cost-effectiveness with long term follow-up. The currently available evidence on the roles of these herbs at molecular level in psoriasis is preliminary.

Clinical Observation on Herb-partitioned Moxibustion on Navel Combined with Yishen Tongluo Prescription in Treatment of Infertility Induced by Idiopathic Asthenozoospermia with Kidney-Yang Deficiency and Collateral Obstruction Syndrome / 中国实验方剂学杂志

ObjectiveTo observe the clinical efficacy of herb-partitioned moxibustion on the navel combined with Yishen Tongluo prescription in the treatment of infertility induced by idiopathic asthenozoospermia （iAZS） with kidney-Yang deficiency and collateral obstruction syndrome and its effect on sperm DNA damage and superoxide dismutase （SOD） in the seminal plasma. MethodsA total of 112 eligible patients who met the inclusion criteria were randomly divided into an observation group （56 cases） and a control group （56 cases）. The patients in the observation group were treated with herb-partitioned moxibustion on the navel combined with Yishen Tongluo prescription，while those in the control group received levocarnitine oral liquid. The primary observation indicators included spouse pregnancy rate，progressive motility （PR），and total sperm motility，and the secondary observation indicators included sperm DNA fragmentation index （DFI），SOD in the seminal plasma， and improvement of TCM syndromes. The treatment cycle was 12 weeks. Before and after treatment，the PR，total sperm motility，sperm DFI，SOD in the seminal plasma， and TCM syndrome scores were recorded. The patients were followed up for 12 weeks and the pregnancy status of spouses within 24 weeks （half a year） was recorded. The clinical efficacy of the two groups was evaluated. ResultThe pregnancy rate of spouses in the observation group was 15.69% （8/51）， higher than 3.85% （2/52） in the control group （χ2=4.118，P<0.05）. The total effective rate of the observation group was 88.24%（45/51）， superior to 69.23% （36/52）in the control group （Z=-3.402，P<0.01）. After treatment， PR， total sperm motility，sperm DFI， SOD in the seminal plasma， and TCM syndromes of the two groups were improved compared with those before treatment （P<0.05）， and the observation group was superior to the control group （P<0.05）. ConclusionHerb-partitioned moxibustion on the navel combined with Yishen Tongluo prescription in the treatment of iAZS-induced infertility patients with kidney-Yang deficiency and collateral obstruction syndrome can increase PR，total sperm motility， and SOD level in the seminal plasma， reduce sperm DFI，improve the TCM symptoms of patients， and improve the pregnancy rate of spouses. The mechanism may be attributed to the fact that this treatment can increase the SOD level in the seminal plasma of patients，enhance the body's antioxidant function，protect sperm from oxidative stress damage，and reduce sperm DFI.

Research progress in the intervention of Chinese herb monomers on diabetic retinal neurodegeneration / 国际眼科杂志(Guoji Yanke Zazhi)

Diabetic retinopathy(DR)has been traditionally considered a purely microvascular disease in the retina. Currently, mainstream therapies focus only on advanced vascular complications and a single molecular target-vascular endothelial growth factor(VEGF). However, the research is shifting towards a more comprehensive view that DR is a neurovascular disease caused by neurovascular unit(NVU)injury. In the early stage of DR, diabetic retinal neurodegeneration(DRN)dominates and may precede the retinal microvascular abnormalities. Moreover, neuronal apoptosis can further lead to microvascular injury and blood-retinal barrier(BRB)disruption. Therefore, it makes sense to develop new therapeutic strategies to prevent or reverse DRN. However, no drug targeting DRN has been approved for clinical use. In recent years, it has become a trend to study the protective effect of traditional Chinese medicine on the retina. The primary research focuses on Chinese herb monomers. This article reviews the research status of representative monomers in DRN to provide references for the early treatment of DR and development of new drugs.

Chemical constituents from whole herb of Hedyotis scandens / 中国中药杂志

This study aimed to investigate the chemical constituents in the water extract of the whole herb of Hedyotis scandens by silica gel, ODS, and MCI column chromatographies together with preparative high-performance liquid chromatography(HPLC). The structures of isolated constituents were identified by NMR, HR-ESI-MS, etc. Thirteen compounds were isolated and identified as methyl 4-benzoyloxy-3-methoxybenzeneacetate(1), 4-benzoyloxy-3-methoxybenzeneacetic acid(2), 3-(4-hydroxy-3-methoxyphenyl)-propanoic acid(3), salicylic acid(4), 3-hydroxy-4-methoxypyridine(5), syringic acid(6), hydroxycinnamic acid(7),(R)-6-methyl-4,6-bis(4-methylpent-3-enyl)cyclohexa-1,3-dienecarbaldehyde(8), 1,2-bis(4-hydroxy-3-methoxyphenyl)-1,3-propanediol(9), 1H-indole-3-carboxaldehyde(10), isoscopoletin(11), syringaresinol(12), and pinoresinol(13). Among them, compounds 1 and 2 were new phenolic acid compounds, compounds 3-5, 8-11, and 13 were isolated from this genus for the first time, and compounds 6, 7, and 12 were obtained from H. scandens for the first time. The activity test showed that compounds 1 and 10 had a certain inhibitory effect on Mycobacterium smegmatis, with MIC_(50) values of 58.5 and 33.3 μg·mL~(-1), respectively.

Mechanism of Astragali Radix-Curcumae Rhizoma in treating gastric cancer based on network pharmacology and experimental verification / 中国中药杂志

This study aims to investigate the mechanism of Astragali Radix-Curcumae Rhizoma(HQEZ) in the treatment of gastric cancer based on network pharmacology. Further, the SGC7901 cell model of gastric cancer was employed to validate the efficacy and key targets of the herb pair. Firstly, the CCK-8 assay was employed to evaluate the direct effect of HQEZ on the proliferation of gastric cancer SGC7901 cells. Then, network pharmacology methods were employed to investigate the active ingredients, key targets, and key signaling pathways involved in the treatment of gastric cancer with HQEZ. The results showed that HQEZ contained 18 potential active ingredients, such as quercetin, naringenin, and curcumin. The results of gene ontology(GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment suggested that the main targets of HQEZ in treating gastric cancer were involved in the regulation of protein serine/threonine kinase activity, activation of mitogen-activated protein kinase(MAPK) activity, cysteine-type endopeptidase activity, and negative regulation of protein serine/threonine kinase activity. The hypoxia-inducible factor-1(HIF-1) signaling pathway, ATP-binding cassette(ABC) transporters, cytochrome P450-mediated metabolism of xenobiotics, p53 signaling pathway, and cell apoptosis were key signaling pathways of HQEZ in treating gastric cancer. The cell experiments demonstrated that HQEZ significantly downregulated the expression of ATP-binding cassette subfamily B member 1(ABCB1), epidermal growth factor receptor(EGFR), phosphorylated serine/threonine kinase(p-AKT), hypoxia inducible factor 1 subunit alpha(HIF1A), B-cell lymphoma 2(BCL2), breast cancer susceptibility protein 1(BRCA1), DNA polymerase theta(POLH), ribonucleotide reductase M1(RRM1), and excision repair cross-complementation group 1(ERCC1), and upregulated the expression of tumor protein P53(TP53) and cysteinyl aspartate-specific proteinase(CAPS3). Finally, a multivariate COX regression model was adopted to study the relationship between gene expression and clinical information data of gastric cancer patients in the TCGA database, which demonstrated that the key targets of HQEZ were associated with the poor prognosis in gastric cancer patients. Further feature selection using the LASSO algorithm showed that EGFR, HIF1A, TP53, POLH, RRM1, and ERCC1 were closely associated with the survival of gastric can-cer patients. In conclusion, HQEZ regulates the expression of genes involved in DNA repair, survival, and apoptosis in gastric cancer cells via multiple targets and pathways, assisting the treatment of gastric cancer.

Observation of the therapeutic effect of Tongyuan needling combined with jingyu herb-separated moxibustion on recurrent implantation failure of kidney deficiency and blood stasis / 中国针灸

OBJECTIVES@#To observe the therapeutic effect of Tongyuan needling combined with jingyu herb-separated moxibustion on the patients with recurrent implantation failure (RIF) of kidney deficiency and blood stasis undergoing frozen embryo transfer of the conventional hormone replacement therapy cycle.@*METHODS@#Sixty RIF of kidney deficiency and blood stasis patients who planned for frozen embryo transfer were randomly divided into a combined treatment group (30 cases) and a western medication group (30 cases). In the western medication group, the conventional hormone replacement therapy was performed for endometrial preparation during transfer cycle. On the basis of treatment as the western medication group, in the combined treatment group, Tongyuan needling combined with jingyu herb-separated moxibustion was adopted. Regarding tongyuan needling, the acupoint prescription for Tongdu Tiaoshen (promoting the governor vessel and regulating the spirit, e.g. Dazhui [GV 14], Ganshu [BL 18], Shenshu [BL 23] and back-shu points) and that for Yinqi Guiguan (conducting qi back to the primary, e.g. Zhongwan [CV 12], Qihai [CV 6], Guanyuan [CV 4] and front-mu points) were selected. Acupuncture was delivered at these two prescriptions alternatively each time. After acupuncture, the herb-separated moxibustion (in which, the herbal powder was prepared with the modified Yangjing Zhongyu decoction for cultivating the kidney essence and promoting pregnancy) was operated at Shenque (CV 8). This combined therapy was delivered once every two days, 3 sessions a week till the day of embryo transfer. The pregnancy outcomes (positive rate of human chorionic gonadotropin [β-HCG] and clinical pregnancy rate) were compared between the two groups, as well as the TCM syndrome score, serum estradiol (E2) and progesterone (P) levels, endometrial thickness and type, endometrial blood flow index (pulsatility index [PI], resistance index [RI]) before and after treatment.@*RESULTS@#After treatment, the clinical pregnancy rate of the combined treatment group was 40.0% (12/30), higher than that of the western medication group (16.7%, 5/30, P<0.05); and the difference in the positive rate of β-HCG was not significant statistically between the two groups (P>0.05). After treatment, the serum levels of E2 and P were elevated (P<0.05), the endometrial thickness was thickened (P<0.05); the scores of TCM syndrome, and the levels of PI and RI were reduced (P<0.05) when compared with those before treatment in the two groups. The proportion of type A endometrium increased compared with that before treatment in the combined treatment group (P<0.05). Except the levels of E2 and P, the above indexes in the combined treatment group were superior to the western medication group (P<0.05).@*CONCLUSIONS@#On the basis of frozen embryo transfer of conventional hormone replacement cycle, the intervention of Tongyuan needling combined with jingyu herb-separated moxibustion can effectively relieve the clinical symptoms, increase the endometrial blood flow and its thickness, and improve the endometrial receptivity, thereby ameliorate pregnancy outcomes in RIF patients of kidney deficiency and blood stasis.

Research advances on extracellular vesicles-based regulation by traditional Chinese medicines and the relationship with TCM "Qi" / 药学学报

Extracellular vesicles (EVs) are an important type of active microvesicles. EVs encapsulate and transfer functional substances such as miRNAs, transcription factors and proteins, which are important vectors for cell communication and organ dialogue. In recent years, studies have shown that quite a number of Chinese medicinal herbs have the pharmacological effect of regulating EVs, and play a unique trans-organ and remote role in the treatment of diseases. Some Chinese medicinal herbs also contain plant-derived EVs themselves, which can be directly involved in the treatment of diseases. As one of the core theories of raditional Chinese medicines (TCM), Qi plays a variety of important roles in the physiological and pathological processes of human body and pharmacology. However, the scientific connotation of Qi′s role and the potential material carrier are still unclear. The latest research suggests that the effect of EVs is potentially related to that of Qi. Therefore, this paper reviews the effect of Qi nourishing Chinese medicinal herbs in regulating EVs in the treatment of cardiovascular diseases, nervous system diseases, liver diseases, renal diseases, malignant tumors and other diseases in recent years. EVs may play an important role in the pharmacological effect of some Chinese medicinal herbs in the treatment of diseases as an intermediary substance. EVs have the characteristics of long-distance transportation, which is consistent with the movement of Qi in TCM. EVs carry a variety of functional molecules, which is consistent with the function of Qi. As the potential material basis of Qi in TCM, the function of EVs is worth further study.

Functions of Scutellariae Radix， Coptidis Rhizoma， and Phellodendri Chinensis Cortex in Materia Medica and Treatise on Febrile and Miscellaneous Diseases / 中国实验方剂学杂志

Scutellariae Radix， Coptidis Rhizoma， and Phellodendri Chinensis Cortex are three commonly used Chinese herbal medicines， and their application in classic famous prescriptions cannot be fully explained by the triple energizer classification method. This study reviewed the ancient materia medica works and elaborated on the functions of the three herbal medicines before the Song dynasty and after the Jin dynasty. The works before the Song dynasty mainly introduced the diseases treated by the three herbal medicines according to the Shennong's Classic of Materia Medica（《神农本草经》）， and the works after the Jin dynasty mainly expounded the indications of the three medicines in the Shennong's Classic of Materia Medica according to the new medical theory. Although all the three herbal medicines can treat heat syndrome， digestive system diseases， skin and mucosa diseases， they act on different targets. Scutellariae Radix can regulate Qi stagnation and reverse caused by the fire syndrome. Coptidis Rhizoma can treat excess fire and purulent bloody stool caused by the deficiency of Zang-fu organs. Phellodendri Chinensis Cortex mainly treats the diseases of the intestine and reproductive system and can kill parasites. In addition， this paper summarized the descriptions about the functions of Scutellariae Radix in eliminating blood blockage， Coptidis Rhizoma in protecting the intestine， and Phellodendri Chinensis Cortex in clearing the liver in ancient books. According to the sentences in the Treatise on Febrile and Miscellaneous Diseases（《伤寒杂病论》）， the application of Scutellariae Radix in Chaihu prescriptions， Coptidis Rhizoma in Baitouweng Decoction， and Phellodendri Chinensis Cortex in Zhizi Baipi Decoction confirms to the indications of the three medicines in the materia medica works before the Song Dynasty. The existing clinical and pharmacological research results confirm the indications of the three herbal medicines in the ancient works. The clinical application of the three medicines should refer to the materia medicia works before the Song dynasty， so as to achieve precise medication.

Effects of christina loosestrife and snowbellleaf tickclover herb on kidney calcium oxalate calculi related metabolites in rats / 国际外科学杂志

Objective:To compare the specific mechanism and effects between christina loosestrife and snowbellleaf tickclover herb on kidney calcium oxalate calculi in rats.Methods:A total of 54 SPF grade SD male rats were fed adaptically for 1 week to 180-200 g, the models of rats with kidney calcium oxalate calculi were established by intragastric administration with glycol, and divided into nine groups according to random number table method and controlled, which were healthy control group (group A), positive control group (model group, group B), low, medium and high doses of christina loosestrife groups (C1, C2, C3, 3 groups), low, medium and high doses of snowbellleaf tickclover herb groups (D1, D2, D3, 3 groups), therapeutic control group (potassium sodium hydrogen citrate group, group E), 6 rats in each group. After 4 weeks, samples were collected to determine the urine and serum biochemical indexes of each group, and Von Kossa staining was used to detect kidney calcium oxalate crystals. Calcium oxalate crystal deposition in kidney tissues of rats was observed under polarization microscope, and the difference of efficacy between the two drug effects was determined by the percentage of positive area in photos and the urine and serum biochemical indexes. The measurement data were expressed as mean ± standard deviation ( ± s), one-way analysis of variance was used for comparison between groups, and SNK- q test was used for comparison between two groups. Kruskal-Wallis test was used to compare crystal formation between groups. Results:Compared with the positive control group and christina loosestrife groups, high dose of snowbellleaf tickclover herb could significantly reduce serum creatinine level ( P<0.01), the mean serum creatinine of rats with christina loosestrife was (86.70±11.49) μmol/L, that of rats with snowbellleaf tickclover herb was (70.72±9.08) μmol/L, the difference was statistically significant ( P<0.01). High dose of christina loosestrife and snowbellleaf tickclover herb could significantly increase urinary magnesium and decrease serum urea levels, and there was no statistical significance between them ( P>0.05). Compared with the positive control group, high dose of christina loosestrife ( P<0.000 1) and snowbellleaf tickclover herb ( P<0.000 1) could both inhibit the formation of calcium oxalate crystals and protect the kidney of rats, and there was no statistical significance between the two effects ( P>0.05). The levels of urine pH value could not be increased, while the levels of urinary calcium urinary oxalic acid and 24 h urine volume, serum calcium, serum phosphorus, serum magnesium, blood uric acid and content of kidney oxalate could not be decreased significantly after using these two drugs. Conclusion:Snowbellleaf tickclover herb is better than christina loosestrife in preventing recurrence of kidney calcium oxalate calculi and protecting renal function.

Sorting and Elaborating on the Combination Theory of Herb Pairs / 中医杂志

@#As the smallest combination unit of Chinese medicinals， herbal pairs serve as the bridge between medicinals and formulas， whose combination theory reflects the basic characteristics of Chinese medicinals combination and the core essence of prescription composition. Simultaneously， as a key combination of medicinals in clinical treatment of diseases， syndromes， and symptoms， herbal pairs are the main form of clinical medication in traditional Chinese medicine （TCM） as well as the characteristic advantage of treating diseases. This article summarized that “mutual complement of medicinals of same or antagonism flavor and nature” theory is the theoretical origin， and efficacy-enhancement and toxicity-attenuation is the core purpose of the combination of herbal pairs. The property theory of Chinese medicinals and the thought of differentiation and treatment are the main basis of the combination of herbal pairs， and pertinence and flexibility are the key points in clinical application. All mentioned above are expected to provide theoretical guidance for the clinical use and modern research of herbal pairs.

Comparative analysis of clinical diagnosis and treatment guidelines for drug-induced liver injury at home and abroad / 中华肝脏病杂志

Drug-induced liver injury influencing factors are complex and have diverse clinical manifestations. Simple and reliable diagnostic methods are still deficient, and further classification of toxicological mechanisms is required. There are numerous pertinent discrepancies between domestic and international guidelines aimed at drug-induced liver injury diagnosis and treatment, with partial to no consensus on the content. The American Gastroenterological Association's 2021 Clinical Guidelines, the Asia-Pacific Association for the Study of the Liver's 2021 Consensus Guidelines, the Council for International Organizations of Medical Sciences' 2020 International Consensus, the European Society's Hepatology Committee's 2019 Clinical Practice Guidelines, and the 2015 Chinese Medical Association Guidelines are five influential clinical guidelines on drug-induced liver injury at home and abroad. The epidemiology, risk factors, diagnosis and evaluation, treatment management, and other contents, particularly traditional Chinese medicine, were compared and analyzed using other relevant consensus opinions or guidelines in order to improve understanding and provide a reference for clinical diagnosis and treatment of drug-induced liver injury.

Integration of plasma metabolomics and spectrum-effect correlation for profiling the mechanism and pharmacodynamic substances on attenuating hepatic fibrosis of Bupleuri Radix and Paeoniae Radix Alba before and after vinegar-processing and compatibility / 药学学报

Plasma metabolomics based on UHPLC-Q-TOF-MS/MS technique was developed for profiling the mechanism on attenuating hepatic fibrosis of Bupleuri Radix (BR) and Paeoniae Radix Alba (PRA) before and after vinegar-processing and compatibility, and to screen potential pharmacodynamic substances by spectrum-effect correlation method in this study. Firstly, SD rats with CCl4-induced hepatic fibrosis were used as an in vivo model. The blood and tissue samples were collected for the analyses of pharmacodynamic indexes and plasma metabolomics after six weeks’ administration of BR, vinegar-processed BR (VPBR), PRA, vinegar-processed PRA (VPPRA), BR-PRA herb-pair, and VPBR-VPPRA herb-pair. The experiment was approved by the experimental animal ethics committee from Nanjing University of Chinese Medicine (No.202103A002). The results of pharmacodynamics indicated that the levels of alanine aminotransferase (ALT, P < 0.01), aspartate aminotransferase (AST, P < 0.01), and hydroxyproline (HYP, P < 0.01) were decreased significantly, while the level of glutathione peroxidase (GSH-Px, P < 0.05) was increased obviously after administration of all treatment groups. Next, UHPLC-Q-TOF-MS/MS was performed to characterize the endogenous metabolites. A total of 20 differential endogenous metabolites related to the pathogenesis of hepatic fibrosis were identified in positive and negative ion modes, mainly involving five metabolic pathways of retinol metabolism, glycerol phospholipid metabolism, glyceride metabolism, fatty acid biosynthesis, and arachidonic acid metabolism. Meanwhile, a concept named correction rate was introduced to evaluate the back-regulation effects of all treatment groups on differential metabolites, and 10 differential metabolites were corrected by all treatment groups. The correction effects of the vinegar-processed herb groups were better than those of the crude ones, and the correction effects of the herb-pair groups were better than those of the single ones. Interestingly, the best correction effect was found in the VPBR-VPPRA herb-pair group, which further verified the efficacy improvement through vinegar-processing and compatibility. Partial least square method and VIP analysis combined with spectrum-effect correlation were applied for screening pharmacodynamic markers, and 38 ingredients with higher correlation with four classical pharmacodynamic indexes (ALT, AST, HYP, and GSH-Px) were identified as pharmacodynamic markers of the anti-hepatic fibrosis effects of BR and PRA before and after vinegar-processing and compatibility. The results of the investigation could not only lay a foundation for clarifying the pharmacodynamic materials and mechanism of vinegar-processing and compatibility of BR and PRA in the treatment of hepatic fibrosis as well as provide a theoretical basis for demonstrating the scientific connotation of processing and compatibility, but also provide a reference for further drug design and development of BR and PRA in clinic.

Textual Research on Tibetan Medicinal Herb Lamiophlomis Herba / 中国实验方剂学杂志

Lamiophlomis Herba， one of the medicinal herbs commonly used by the Tibetan ethnic minority， has the effect of activating blood， stopping bleeding， dispelling wind， and relieving pain and is frequently used to treat trauma， traumatic bleeding， rheumatic arthralgia， and dampness and dampness-heat. By a review of ancient Tibetan medicine classics， materia medica classics， and modern literature， this paper systematically analyzed the name， nature， taste， original plant， medicinal part， harvest， processing， efficacy， and indications of Lamiophlomis Herba. The textual research showed that Lamiophlomis Herba was first recorded in the Somaratsa （《月王药诊》） in the middle of the eighth century. This medicinal herb was mainly recorded with a plain and warm nature and a sweet， bitter， and astringent taste. The herb was recorded as non-toxic in other books except the Tibetan Medicinal Plants in Gannan of Qinghai-Tibet Plateau （《青藏高原甘南藏药植物志》）. In the books of the past dynasties， the aboveground part of Lomiophlomis rotatd was used as medicine. In addition， there were also records of using the whole herbs of Ajuga ovalifolia， A. ovalifolia var. calantha， and Oreosolen wattii as the medicine. In ancient times， the herb was mainly harvested before Frost's Descent in the 8th-9th months of the lunar calendar， while it was mainly harvested during the flowering-fruiting stage in autumn in modern times. Due to the decreased reserve of Lamiophlomis Herba， the medicinal part evolved from whole herb or fresh leaves to the aboveground part. According to the ancient and modern records， this herb mainly has the functions of nourishing bone and marrow， eliminating dampness and dampness-heat， stopping bleeding， and relieving pain. In ancient times， it was used for treating parasitic diseases， menostaxis， spermatorrhea， diarrhea， and nourishing the body. This paper aims to provide a basis for further development and study of Lamiophlomis Herba through the textual research.

Activation of PXR causes drug interactions with Paxlovid in transgenic mice

Paxlovid is a nirmatrelvir (NMV) and ritonavir (RTV) co-packaged medication used for the treatment of coronavirus disease 2019 (COVID-19). The active component of Paxlovid is NMV and RTV is a pharmacokinetic booster. Our work aimed to investigate the drug/herb-drug interactions associated with Paxlovid and provide mechanism-based guidance for the clinical use of Paxlovid. By using recombinant human cytochrome P450s (CYPs), we confirmed that CYP3A4 and 3A5 are the major enzymes responsible for NMV metabolism. The role of CYP3A in Paxlovid metabolism were further verified in Cyp3a-null mice, which showed that the deficiency of CYP3A significantly suppressed the metabolism of NMV and RTV. Pregnane X receptor (PXR) is a ligand-dependent transcription factor that upregulates CYP3A4/5 expression. We next explored the impact of drug- and herb-mediated PXR activation on Paxlovid metabolism in a transgenic mouse model expressing human PXR and CYP3A4/5. We found that PXR activation increased CYP3A4/5 expression, accelerated NMV metabolism, and reduced the systemic exposure of NMV. In summary, our work demonstrated that PXR activation can cause drug interactions with Paxlovid, suggesting that PXR-activating drugs and herbs should be used cautiously in COVID-19 patients receiving Paxlovid.

Intervention effect of Chuanxiong-Chishao herb pair on circRNA/lncRNA expression profile in a myocardial infarction-atherosclerosis model / 中国中药杂志

This study aimed to explore the intervention effect of Chuanxiong-Chishao herb pair(CX-CS) on a myocardial infarction-atherosclerosis(MI-AS) mouse model and investigate its effect on the expression profile of circular RNAs(circRNAs)/long non-coding RNAs(lncRNAs) in ischemic myocardium and aorta. Sixty male ApoE~(-/-) mice were randomly assigned to a model group, high-, medium-, and low-dose CX-CS groups(7.8, 3.9, and 1.95 g·kg~(-1)), and a positive drug group(metoprolol 26 mg·kg~(-1) and simvastatin 5.2 mg·kg~(-1)), with 12 mice in each group. Male C57BL/6J mice were assigned to the sham group. The mice in the model group and the groups with drug intervention were fed on a high-fat diet for 10 weeks, followed by anterior descending coronary artery ligation. After that, the mice were fed on a high-fat diet for another two weeks to induce the MI-AS model. The mice in the sham group received normal feed, followed by sham surgery without coronary artery ligation. Mice in the groups with drug intervention received CX-CS or positive drug by gavage for four weeks from the 9th week of high-fat feeding, and those in the model group and the sham group received an equal volume of normal saline. Whole transcriptome sequencing was performed on the heart and aorta tissues of the medium-dose CX-CS group, the model group, and the sham group after administration. The results showed that the medium-and high-dose CX-CS groups showed improved cardiac function and reduced myocardial fibrosis area, and the medium-dose CX-CS group showed significantly reduced plaque area. CX-CS treatment could reverse the expression of circRNA＿07227 and circRNA＿11464 in the aorta of AS model and circRNA expression(such as circRNA＿11505) in the heart of the MI model. Differentially expressed circRNAs between the CX-CS-treated mice and the model mice were mainly enriched in lipid synthesis, lipid metabolism, lipid transport, inflammation, and angiogenesis in the aorta, and in angiogenesis, blood pressure regulation, and other processes in the heart. CX-CS treatment could reverse the expression of lncRNAs such as ENSMUST00000162209 in the aorta of the AS model and TCONS＿00002123 in the heart of the MI model. Differentially expressed lncRNAs between the CX-CS-treated mice and model mice were mainly enriched in lipid metabolism, angiogenesis, autophagy, apoptosis, and iron death in the aorta, and in angiogenesis, autophagy, and iron death in the heart. In summary, CX-CS can regulate the expression of a variety of circRNAs and lncRNAs, and its intervention mechanism in coronary heart disease may be related to the regulation of angiogenesis and inflammation in ischemic myocardium, as well as lipid metabolism, lipid transport, inflammation, angiogenesis in AS aorta.

Optimization of extraction process of Chuanxiong Rhizoma-Gastrodiae Rhizoma based on network pharmacology and multi-index orthogonal test / 中国中药杂志

To optimize the extraction process of Chuanxiong Rhizoma-Gastrodiae Rhizoma herb pair by network pharmacology combined with analytic hierarchy process(AHP)-entropy weight method and multi-index orthogonal test. The potential active components and targets of Chuanxiong Rhizoma-Gastrodiae Rhizoma were screened by network pharmacology and molecular docking, and the process evaluation indexes were determined with reference to the Chinese Pharmacopoeia(2020 edition). The core components of Chuanxiong Rhizoma-Gastrodiae Rhizoma were determined as gastrodin, parishin B, parishin C, parishin E, ferulic acid, and 3-butylphthalide. With the extraction volume of each indicator and yield of dry extract as comprehensive evaluation indicators, the extraction conditions were optimized by the AHP-entropy weight method and orthogonal test as the ethanol volume of 50%, the solid-liquid ratio of 1∶8(g·mL~(-1)), extraction for three times, and 1.5 h each time. Through network pharmacology and molecular docking, the process evaluation index was determined, and the optimized process was stable and reproducible for the extraction of Chuanxiong Rhizoma-Gastrodiae Rhizoma herb pair, which could provide reference for in-depth research.