Ephedra Sinica Research Articles

Ephedrate A, a new phenol compound from the root of Ephedra sinica

ObjectiveTo study the chemical constituents of the roots of Ephedra sinica Stapf. MethodsThe roots of E. sinica were extracted with 90% ethanol and isolated and purified by column chromatography on silica gel, Sephadex LH 20, and semipreparative RP-HPLC. All the compounds were identified based on spectral analysis (including MS, 1H-NMR and 13C-NMR, and 2D NMR) and compared with the reported literature. Their cytotoxicities were evaluated against three human cancer cell lines. ResultsTwo compounds were isolated from the roots of E. sinica and identified as (E)-eicosyl 3,4-dihydroxy-5-methoxycinnamate (1) and (E)-hexadecyl-ferulate (2). ConclusionCompound 1 was a new phenol named ephedrate A, and compound 2 was newly isolated from this plant. These two compounds showed no obvious cytotoxic activity, and their medicinal activities need to be studied further.

Studying the nature of ascending-descending-floating-sinking of Chinese medicines based on gonadotropin-releasing hormone.

to explore the nature of ascending-descending-floating-sinking of Traditional Chinese Medicine on normal rats using gonadotropin-releasing hormone (GnRh). Normal male Sprague-Dawley rats were orally administered six floating Chinese medicines and seven sinking Chinese medicines for 14 d. then, GnRh and relevant indicators were detected. Initially, the different effects of floating and sinking drugs on the body were explored. To verify the effects of floating and sinking drugs on the body, normal rats were orally administered Mahuang (Herba Ephedra Sinica) and Tinglizi (Semen Lepidii Apetali) for 14 d. Then, GnRh antagonists were administered. We observed the changes of relevant indicators and clarified the correlation between GnRh and the laws of floating and sinking. Floating Chinese medicines significantly increased the testicular coefficients; GnRh level in the serum; the protein level of GnRh receptor (GnRhR) in the testis; and the mRNA levels of androgen receptor (AR), small C-terminal domain phosphatase (SCP) 3, SCP2, SYCE1, SMC1B, SMC3, and Rec8 (P < 0.01 or < 0.05). Sinking Chinese medicines did not react similarly, while GnRh antagonists blocked the regulatory effect of Mahuang (Herba Ephedra Sinica) but did not affect Tinglizi (Semen Lepidii Apetali). GnRh may be closely related to the nature of ascending-descending-floating-sinking of Chinese medicine. Floating Chinese medicines may promote their medicinal properties by regulating GnRH level; however, sinking Chinese medicines did not affect GnRh level.

SUPERVISION OF TRADITIONAL MEDICINES CONTAINING UNDECLARED SUBSTANCE: ANALYSIS OF INDONESIAN FDA MONITORING DATA FOR 2012 - 2021

Background: At a time when people believe in the efficacy and minimal risk of traditional medicines, government agencies that oversee traditional medicines often find chemicals that are intentionally added to traditional medicines. The purpose of this study is to present the findings of Undeclared Substance that have been added to traditional medicines for ten years, to analyze their relevance to the real situation related to diseases or health problems in Indonesia, and to examine the violations of related policies. Methods: This study used an observational design based on quantitative and qualitative data and analyzed descriptively. Quantitative data based on Traditional Medicines Monitoring data are published through the website (www.pom.go.id) in the category of public warning OT-BKO in 2012-2021. Further analysis, conducted in-depth interviews to explore the root cause of the problem at the level of policy makers. Documents and literature review were conducted to analyze the findings. Interviews with policy makers were also conducted to confirm findings and explore problems that were not obtained from documents and literature. Results: For ten years, Paracetamol was the most common type of Undeclared Substance found every year in traditional medicines. This is relevant to the high number of complaints related to indications for the use of Paracetamol, both from reports from health facilities and results from household surveys. Meanwhile, the findings of the Ephedrine Undeclared Substance - with indications for reducing respiratory disorders - only appeared in 2021. These findings are not only relevant to the COVID-19 pandemic and the entry of traditional medicines from foreign aid, which also contain Ephedra sinica. The Undeclared Substance' findings are inconsistent with the objectives of a number of regulations ranging from those related to traditional medicine to consumer protection. Conclusion: The findings of Undeclared Substance on traditional medicine were relevant to public health problems at that time. The emergence of traditional medicines with Ephedra shows that domestic producers do not understand the safety of traditional medicines. In addition, the existing policies and violations of these policies have not been understood by traditional medicine manufacturers.

Transcriptional Regulatory Mechanism of Differential Metabolite Formation in Root and Stem of Ephedra sinica.

Ephedra sinica, a well-known Chinese medicinal plant, is characterized as having the opposite medicinal effect among its root and stem. However, there is a lack of understanding to differentiate the active components present in the root and stem of E. sinica, as well as the molecular mechanisms underlying the formation of the differential compounds, which has significantly hampered the further development and utilization of E. sinica resource. In this study, forty-five differential metabolic markers are affiliated to alkaloids, flavonoids, terpenoids, and organic acids between root and stem of E. sinica, and sixty genes of key enzymes are involved in their biosynthesis distributed in metabolic pathway branches such as phenylalanine metabolism, flavonoid biosynthesis and phenylpropane biosynthesis, based on combination non-targeted metabolome with transcriptome technologies. The finding revealed that the expression activity changes of these enzyme genes had a direct impact on the distinction of differential metabolic markers in the root and stem of E. sinica. This study will help to understand the molecular mechanism of the differentiation and biosynthesis of the primary active metabolites in the root and stem of E. sinica, providing a theoretical foundation for its quality control and promotion in cultivation.

Mahuang (herbaceous stem of Ephedra spp.): chemistry, pharmacodynamics, and pharmacokinetics

The Chinese medicinal herb Mahuang is herbaceous stem of Ephedra sinica, E. intermedia, or E. equisetina(Family, Ephedraceae). In China, Mahuang has been used, all the way over a millennium, as a key component herb of many herbal medicines for management of epidemics of acute respiratory illness and is also used in officially recommended herbal medicines for COVID-19. Mahuang is the first-line medicinal herb for cold and wheezing and also an effective diuretic herb for edema. However, Mahuang can also exert significant adverse effects. The key to safety and effectiveness is rational and precise use of the herb. In this review article, we comprehensively summarize chemical composition of Mahuang and associated differences in pharmacognosy, pharmacodynamics and pharmacokinetics of Mahuang compounds, along with the adverse effects of Mahuang compounds and products. Based on full understanding of how Mahuang is used in Chinese traditional medicine, systematic research on Mahuang in line with contemporary standards of pharmaceutical sciences will facilitate promoting Chinese herbal medicines to become more efficient in management of epidemic illnesses, such as COVID-19. To this end, we recommend research on Mahuang of two aspects, i.e., pharmacological investigation for its multicompound-involved therapeutic effects and toxicological investigation for clinical manifestation of the adverse effects, chemicals responsible for the adverse effects, and conditions for safe use of the herb and the herb-containing medicines.

Dietary supplements for obesity.

Obesity and associated complications including diabetes, cardiometabolic dysfunction, disability, malignancy and premature mortality are considered epidemic. Research on obesity is therefore of worldwide importance. The development of obesity is a multifactorial phenomenon with contributions from biological, behavioral, genetic and environmental factors. Obesity and its associated issues require various lifestyle modifications and treatment options such medication, exercise, diet, surgery, pharmacological therapy and dietary supplements. Dietary supplements are considered an attractive alternative to traditional therapy due to their low toxicity profile and their accessibility to the general population. Dietary supplements may include one or more dietary ingredients. In this narrative review, we analyze the effects on obesity and obesity-related issues of various natural components. For example, there are a myriad of supplements that have been used as dietary supplements for weight loss such as minerals, vitamins, amino acids, metabolites, herbs, and plant extracts. This narrative review aims to present the benefits and side-effects of several ingredients of dietary supplements for weight loss and treatment of obesity. In particular, the mechanism of action, results of clinical trials, and possible side effects will be presented for the following ingredients: β-Glucans, bitter orange, calcium, vitamin D, chitosan, chromium, cocoa, coleus forskohlii, conjugate linoleic acid, ephedra sinica, fucoxanthin, garcinia cambogia, glucomannan, green coffee, green tea, guar gum, raspberry, hoodia gordonii, irvingia gabonensis, phenylpropylamine, pyruvate, white kidney bean.

The Ameliorative Effect of Mahuang Fuzi and Shenzhuo Decoction on Membranous Nephropathy of Rodent Model is Associated With Autophagy and Wnt/β-Catenin Pathway.

The increased incidence of membranous nephropathy (MN) has made it the most common pathological type of primary nephrotic syndrome in adults in China. According to the theory of Traditional Chinese Medicine (TCM), Mahuang Fuzi (Chinese ephedra and Radix Aconiti Lateralis Preparata) and Shenzhuo Decoction (MFSD) could be used to treat such diseases. We treated patients of MN with MFSD, and observed comparable efficacy to glucocorticoid and/or immunosuppressants. In this study, we observed the therapeutic effect of MFSD on the rat model of passive Heymann nephritis (PHN), a classical MN model. Our results showed that MFSD treatment significantly reduced urinary protein level and podocyte injury in PHN rats, and correspondingly improved renal pathology, with the improvement effect on MN comparable to that of Cyclosporine A (CsA) alone. To explore the potential therapeutical mechanism of MFSD, the main chemical components of MFSD were determined by High-performance liquid chromatography-mass spectrometry (HPLC-MS). There were about 30 active components of MFSD. Next, based on network pharmacology methods, we screened related targets of MSFD on MN, which provided a preliminary understanding of the MFSD bioactive compounds. The clustering analysis showed that its active site might be in the autophagy-related protein and Wnt/β-catenin pathway, which was related to podocyte injury. Finally, we observed an improvement in renal autophagy and a down-regulation of the Wnt/β-catenin pathway after MSFD treatment in a PHN rat model. According to this study, autophagy and Wnt/β-catenin pathway may be potential targets for MFSD in the treatment of MN.

Extract of Ephedra sinica Stapf Induces Browning of Mouse and Human White Adipocytes.

Browning of adipocytes using herbal extracts is an attractive and realistic strategy for obesity treatment. Ephedra sinica Stapf (E. sinica) is an Asian traditional medicine known to activate brown adipocytes. To evaluate the effect of E. sinica (EEs) on the browning of white adipocytes, expression levels of browning markers, including uncoupling protein 1 (UCP1), were determined using qPCR, Western blot, and immunocytochemistry after mature mouse inguinal preadipocyte (mIPA) and human adipose-derived stem cells (hADSCs) were treated with EEs. In addition, mitochondrial activity was determined by analyzing MitoTracker staining, mtDNA copy number, and oxygen consumption rate (OCR). Treatment with EEs suppressed lipid accumulation and expression levels of adipogenic markers, including Pparg, during mIPA differentiation. In mature mIPA and hADSCs browning markers, including Ucp1, were up-regulated by EEs. In addition, EEs increased expression of mitochondrial genes, mtDNA copy number, and OCR. EEs showed a dual function: inhibiting adipogenesis in immature preadipocytes, and promoting thermogenesis via browning in mature white adipocytes. Therefore, E. sinica is a potential herb for regulating energy metabolism by inducing the browning process.

Formulation and Evaluation of Expectorant activity of Poly Herbal Cough Syrup from Traditional Medicinal Plant extracts of North East India

Poly Herbal formulation composed of multi components which produce synergistic effect apart from boost up of body natural immunity. Plants material may contains polysaccharide, mucilage and tannin which are responsible for the synergism of “active principles”. The Poly herbal cough syrup was prepared by mixing of extracts from five different plants namely Ocimum sanctum, Adhatoda vasica, Cinnamomum verum, Cardamomum subulatum and Ephedra sinica in a syrupy base. The evaluation of the formulation was done by determining different physical parameters such as pH, surface tension, total solid content, specific gravity, viscosity, refractive index and expectorant activity of the cough preparation was done on phenol red induced mice model. The pH, surface tension, total solid content, specific gravity, viscosity and refractive index were found to be 4.82, 54.32 dynes/cm, 38.20% w/v, 1.324 (at 250C), 4.68cp and 1.43 respectively. There was a significant increase (P&lt;0.001) in expectorant activity of the formulation at the doses of 300mg/kg and 600mg/kg as compared to the control group. So the herbal formulation could be used to alleviate mucous secretion from bronchial tract.

Phytochemical and Heavy Metal Composition of Various Extracts of Ephedra sinica from Jordan

Phytochemical and Heavy Metal Composition of Various Extracts of Ephedra sinica from Jordan

“Mini-Community” Simulation Revealed the Differences of Endophytic Fungal Communities between the Above- and Below-Ground Tissues of Ephedra Sinica Stapf

“Mini-Community” Simulation Revealed the Differences of Endophytic Fungal Communities between the Above- and Below-Ground Tissues of Ephedra Sinica Stapf

Habitat protection and planning for three Ephedra using the MaxEnt and Marxan models

As renowned species for use in sand fixation and traditional Chinese medicines, Ephedra sinica Stapf, Ephedra intermedia Schrenk ex Mey and Ephedra equisetina Bunge have important ecological and medicinal value. However, although conservation measures have been implemented, the suitable habitat for these species has been shrinking at a remarkable rate in recent years due to climate change and anthropogenic activities. The identification of suitable habitats for these three Ephedra is essential for their protection and cultivation. Thus, this study proposed a new method for planning the best species conservation habitat through fitting errors caused by a single model. The method modeled the current suitable habitats of the three Ephedra species using the MaxEnt model and evaluated the key environmental variables defining the Ephedra distribution based on recorded occurrence data for Xinjiang, Inner Mongolia, Gansu, and Qinghai. The results showed that human activities were the most important environmental parameter affecting the distribution of the three species, and land cover, ground frost frequency and precipitation accounted for an important proportion of the model evaluation. Second, the results obtained with the MaxEnt model were coupled with the finding from the Marxan model to identify priority conservation areas for the three Ephedra species. The results revealed that the most suitable habitats for E. sinica were mainly concentrated in eastern and central Inner Mongolia, E. intermedia was relatively distributed in southern and central Gansu, and the areas of E. equisetina were mainly distributed in northern Xinjiang. The priority conservation areas for E. sinica, E. intermedia, and E. equisetina were 38068.12 km2, 26446.74 km2 and 36360.6 km2, respectively. The comprehensive analysis indicated that be use of MaxEnt coupled with the Marxan model to model the suitable habitat of these Ephedra species eliminates the distribution errors introduced by each model alone. The protection of wild Ephedra should be a priority, and the scale of the artificial planting of Ephedra should be enlarged. Given these results, the three Ephedra species included in our study urgently need to be subjected to targeted conservation management to ensure the renewal of Ephedra communities and to maintain the supply of medicinal materials. This study provides a useful reference for the protection and cultivation of these three Ephedra.

Interactions Between Ephedra sinica and Prunus armeniaca: From Stereoselectivity to Deamination as a Metabolic Detoxification Mechanism of Amygdalin.

Mahuang–Xingren (MX, Ephedra sinica Stapf-Prunus armeniaca L.) is a classic herb pair used in traditional Chinese medicine. This combined preparation reduces the toxicity of Xingren through the stereoselective metabolism of its main active ingredient amygdalin. However, whether stereoselectivity is important in the pharmacokinetic properties of amygdalin either in the traditional decoction or in the dispensing granules is unclear. Amygdalin is hydrolyzed to its metabolite, prunasin, which produces hydrogen cyanide by degradation of the cyano group. A comprehensive study of the metabolic pathway of amygdalin is essential to better understand the detoxification process. In this article, the potential detoxification pathway of MX is further discussed with regard to herb interactions. In this study, the pharmacokinetic parameters and metabolism of amygdalin and prunasin were investigated by comparing the traditional decoction and the dispensing granule preparations. In addition, several potential metabolites were characterized in an incubation system with rat liver microsomes or gut microbial enzymes. The combination of Xingren with Mahuang reduces exposure to D-amygdalin in vivo and contributes to its detoxification, a process that can be further facilitated in the traditional decoction. From the in vitro co-incubation model, 15 metabolites were identified and classified into cyanogenesis and non-cyanogenesis metabolic pathways, and of these, 10 metabolites were described for the first time. The level of detoxified metabolites in the MX traditional decoction was higher than that in the dispensing granules. The metabolism of amygdalin by the gut microbial enzymes occurred more rapidly than that by the rat liver microsomes. These results indicated that combined boiling both herbs during the preparation of the traditional decoction may induce several chemical changes that will influence drug metabolism in vivo. The gut microbiota may play a critical role in amygdalin metabolism. In conclusion, detoxification of MX may result 1) during the preparation of the decoction, in the boiling phase, and 2) from the metabolic pathways activated in vivo. Stereoselective pharmacokinetics and deamination metabolism have been proposed as the detoxification pathway underlying the compatibility of MX. Metabolic detoxification of amygdalin was quite different between the two combinations, which indicates that the MX decoctions should not be completely replaced by their dispensing granules.

Correlation analysis between differential metabolites and bacterial endophytes of Ephedra sinica in different years

Ephedra sinica is widely used in the treatment of diseases due to its rich and diverse pharmacological effects. The quality of E. sinica is various in different years. However, the effect of endophytes on the accumulation of metabolites of E. sinica in different years is still obscure. In this study, the relationship between the ecological succession of bacterial endophytes and metabolite accumulation of E. sinica grown in different years were generally investigated based on 1H NMR and 16 s rDNA sequencing. The results showed that 38 differential marker metabolites existed in E. sinica grown in different years. The distribution and abundance of bacterial endophytes changed during the growth of cultivated E. sinica, and there was remarkable correlation between the dominant endophytes and differential metabolites. This study provides a critical reference in evaluating and monitoring the quality of E. sinica in the process of cultivation, and establish a solid foundation for the use of species interactions to improve the quality of E. sinica in different years.

Combination of Ephedra sinica stems and Terminalia chebula fruits produces new ephedrine derivatives in vivo that diminish the permeability to BBB while retaining airway dilation and hepatoprotective effects

Ethnopharmacological relevanceThe stems of Ephedra sinica and the fruits of Terminalia chebula are combined using in traditional Mongolian medicine formula “Gurigumu-7” for liver diseases. E. sinica stems contains ephedrine with broncho-dilatory activity. However, ephedrine can pass through the blood-brain barrier (BBB) and excite the central nervous system (CNS) to cause insomnia and restlessness. Aim of the studyThe present study was to investigate the structures and bioactivities of new compounds formed in vivo after co-administration of E. sinica stems and T. chebula fruits. Materials and methodsPharmacokinetic investigation was carried out in rats. A parallel artificial membrane permeability measurement system was used to determine BBB permeability. Ex vivo experiments using tracheal rings of guinea pig was performed to examine the tracheal relaxation effect. In vivo hepatoprotective tests were carried out in Tg (fabp10a: dsRed) liver transgenic zebrafish. The fluorescent probe, 2,7-dichlorodihydrofluorescein diacetate, was used to measure reactive oxygen species, and UHPLC-MS was used to determine glutathione concentrations after derivatization with N-ethylmaleimide. ResultsNew ephedrine derivatives (1 and 2) formed in vivo and reached their maximum serum concentrations at 0.5 h after administration of the two herbal drugs. Compounds 1 and 2 showed lower BBB permeability than ephedrine, suggesting that they have less adverse effects on the CNS. Compounds 1 and 2 relaxed the tracheal rings and had strong hepatoprotective effect on transgenic zebrafish with liver specific expression of RFP. Compounds 1 and 2 significantly reduced the level of reactive oxygen species while increasing that of glutathione in thioacetamide-treated zebrafish, which might be the hepatoprotective mechanism. ConclusionThese results provided evidences that the chemical constituents in various herbal drugs in a medicinal formula can interact to generate new compounds with fewer side effects and increased or additive bioactivity.

Stability and Reproducibility of Ephedra sinica Ephedrine Alkaloid Content and Terrestrial Stem Dry Weight.

Dried terrestrial stems of Ephedra sinica are known as 'Ephedra herb.' The pharmacological effects are mainly related to two major ingredients, (-)-ephedrine and (+)-pseudoephedrine (total alkaloids which are defined in Japanese Pharmacopoeia, TA). In this study, in order to aid in cultivation and breeding, the stability of TA content and stem dry weight of 46 E. sinica genets was evaluated from the first year of transplantation to the sixth year. TA content and composition ratio of these genets were stable after the second year, and dry weight was stable after the fourth year. These traits showed high inter-genet variability but low annual variability for each genet. Additionally, rank correlation coefficients of each trait among the genets were high. There was no significant correlation between these traits. Furthermore, to assess the reproducibility of these traits in clones, we evaluated TA content and dry weight of three clonal lines with high TA contents. TA content and composition ratio of the clonal lines were also stable after the second year of transplantation, and dry weight of the clonal lines was also stable after the fourth year. Moreover, TA content and composition ratio in each clonal line were comparable with those of each original genet after the second year. These results suggested that ephedrine alkaloids content and dry weight of E. sinica plants are stable, and that these traits are highly reproducible in clones. Therefore, selection breeding of E. sinica using vegetative propagation can be effective for high and stable quality of Ephedra herb.

Comparison of Volatile Oils and Primary Metabolites of Raw and Honey-Processed Ephedrae Herba by GC-MS and Chemometrics.

Ephedrae Herba (EH) is the terrestrial stem of Ephedra sinica Stapf, E. intermedia Schrenk et C. A. Mey., or E. equisetina Bge, which has been used as a diaphoretic, antiasthmatic, and diuretic. Honey-processed EH (HEH) is a widely used traditional Chinese medicine, and has a better effect of dispersing lung qi and relieving asthma and a lower effect of dispelling cold than raw EH (REH). To understand the differences in volatile oils and primary metabolites between REH and honey-processed HEH, and to provide a reference for elucidating the mechanism behind the effect of this processing. A system data acquisition and mining strategy was designed to investigate the differences in volatiles and primary metabolites between the REH and HEH, based on GC-MS coupled with multivariate statistical analysis, including principal component analysis and orthogonal partial least squares discriminant analysis. Overall, 15 volatile oils and 14 primary metabolites were shown to be potential characteristic markers differentiating REH and HEH. The results may provide a scientific foundation for comprehensively revealing the honey-processing mechanism of EH. Volatile oils and primary metabolites were used to distinguish REH and HEH and elucidate the processing mechanism of EH for the first time.

Pseudoephedrine and its derivatives antagonize wild and mutated severe acute respiratory syndrome-CoV-2 viruses through blocking virus invasion and antiinflammatory effect.

The coronavirus disease 2019 has infected over 150 million people worldwide and led to over 3 million deaths. Severe acute respiratory syndrome (SARS)‐CoV‐2 lineages B.1.1.7, B.1.617, B.1.351, and P.1 were reported to have higher infection rates than that of wild one. These mutations were noticed to happen in the receptor‐binding domain of spike protein (S‐RBD), especially mutations N501Y, E484Q, E484K, K417N, K417T, and L452R. Currently, there is still no specific medicine against the virus; moreover, cytokine storm is also a dangerous factor for severe infected patients. In this study, potential S‐RBD‐targeted active monomers from traditional Chinese medicine Ephedra sinica Stapf (ephedra) were discovered by virtual screening. NanoBiT assay was performed to confirm blocking activities of the screened compounds against the interaction between SARS‐CoV‐2 S‐RBD and angiotensin‐converting enzyme 2 (ACE2). We further analyzed the blocking effect of the active compounds on the interactions of mutated S‐RBD and ACE2 by computational studies. Moreover, antiinflammatory activities were evaluated using qRT‐PCR, enzyme‐linked immune sorbent assay, and Western blot analysis. As a result, pseudoephedrine (MHJ‐17) and its derivative (MHJ‐11) were found as efficient inhibitors disrupting the interactions between ACE2 and both wild and mutated S‐RBDs. In addition, they also have antiinflammatory activities, which can be potential drug candidates or lead compounds for further study.

Mechanism of Wuwei Ganlu in treatment of knee osteoarthritis:a study based on network pharmacology and molecular docking

Wuwei Ganlu, a formula for medicated bath, consists of medicinal materials of Ephedra sinica, Platycladus orientalis, Myricaria squamosa, Artemisia carvifolia, and Rhododendron anthopogonoides, which is effective in inducing perspiration, resisting inflammation, relieving pain, regulating yellow water disease, and activating blood circulation. On this basis, a variety of formulas for Tibetan medicated bath have been derived for the treatment of diseases in internal organs, joints, nerves, etc. Modern studies have confirmed that Wuwei Ganlu has a good therapeutic efficacy on knee osteoarthritis(KOA). The present study explored the mechanism of Wuwei Ganlu in treating KOA based on network pharmacology and molecular docking. Firstly, the chemical components of Wuwei Ganlu were obtained through literature mining and database retrieval, and corresponding potential targets were predicted according to the BATMAN-TCM database. The protein-protein interaction(PPI) network was obtained after the potential targets were input into the STRING database. The network function modules were analyzed by the Molecular Complex Detection(MCODE) algorithm, and the functions of the modules were annotated to analyze the action mode of Wuwei Ganlu. Secondly, the related targets of KOA were collected through the DisGeNET database, and the overlapping targets were confirmed to analyze the mechanism of Wuwei Ganlu in treating KOA. Finally, the key targets were selected for molecular docking with the main components of Wuwei Ganlu to verify the component-target interaction. A total of 550 chemical components and 1 365 potential targets of Wuwei Ganlu were obtained. PPI analysis indicated that this formula could exert the effects of oxidation-reduction, inflammation resistance, bone absorption, bone mineralization, etc. Nineteen common targets were obtained from the intersection of potential targets of Wuwei Ganlu and KOA disease targets. It was found that the Wuwei Ganlu mainly acts on nuclear factor-κB(NF-κB), interleukin-1 beta(IL1β), tumor necrosis factor(TNF), IL6, IL1 receptor antagonist(IL1 RN), and prostaglandin-endoperoxide synthase-2(PTGS2) to treat KOA. Among the 550 chemical components of Wuwei Ganlu, 252 potential active components were docked with TNF and 163 with PTGS2, indicating good binding of the components with potential key targets. The study preliminarily explored the mechanism of Wuwei Ganlu in treating KOA to provide a reference for the further development and utilization of Tibetan medicated bath that has been included in the UN Intangible Cultural Heritage.

Non-ephedrine constituents from the herbaceous stems of Ephedra sinica

Three new flavonoids, ephedroside A (1), ephedroside B (2), ephedroside C (3), together with fifty-four known compounds 4–57 were isolated from the EtOH extract of the herbaceous stems of Ephedra sinica. The structures of these compounds were elucidated by spectroscopic techniques, as well as by comparison with literature data. Thirty-eight of these compounds were isolated from the genus Ephedra for the first time. The antimicrobial activities of eight compounds were tested by measuring the minimum inhibitory concentrations (MIC) against bacteria (both Gram positive and Gram negative) and fungi, and were found to be in the range of 0.105–0.926 mM. Among them, compound 2 showed the best antimicrobial activity against Pseudomonas aeruginosa with MIC value of 0.105 mM.