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Berberine (BBR) is a natural alkaloid, which has played an important role in the field of medicine since its discovery in the late 19th century. However, the low availability of BBR in vivo prevents its full effect. In recent years, a large number of studies confirmed that BBR has a protective effect on the nervous system through various functions, yet the issue of the inability to systematically understand the protection of BBR on the nervous system remains a gap that needs to be addressed. Many existing literature introductions about berberine in neurodegenerative diseases, but the role of berberine in the nervous system goes far beyond these. Different from these literatures, this review is divided into three parts: preparation method, mechanism, and therapeutic effect. Various dosage forms of BBR and their preparation methods are added, in order to provide a reasonable choice of BBR, and help to solve the problem of low bioavailability in treatment. More importantly, we more comprehensively summarize the mechanism of BBR to protect the nervous system, in addition to the treatment of neurodegenerative diseases (anti-oxidative stress, anti-neuroinflammation, regulation of apoptosis), two extra mechanisms of berberine for the protection of the nervous system were also introduced: bidirectional regulation of autophagy and promote angiogenesis. Also, we have clarified the precise mechanism by which BBR has a therapeutic effect not only on neurodegenerative illnesses but also on multiple sclerosis, gliomas, epilepsy, and other neurological conditions. To sum up, we hope that these can evoke more efforts to comprehensively utilize of BBR nervous system, and to promote the application of BBR in nervous system protection.

Herb compatibility is the soul of traditional Chinese Medicine prescriptions. Coptidis rhizoma (CR) (Coptis chinensis Franch., Coptis deltoidea C.Y.Cheng et Hsiao, or Coptis teeta Wall.; family Ranunculaceae), is a well-known herb. The bitter and cold nature of CR can irritate the spleen and stomach, and certain ingredients in CR may trigger allergic reactions. Herb combinations can help alleviate the side effects caused by CR. Through data analysis and literature research, there are many herbs combined with CR have a high frequency, but only a few are currently used as formulae in clinical practice. The results showed that these six herb pairs are usually widely studied or used as prescriptions in the clinic. This paper describes the six herb pairs from the key traditional uses, changes in bioactive constituents, and compatibility effects, especially with Euodiae fructus (family Rutaceae), Scutellariae radix (family Lamiaceae), Magnoliae Officinalis cortex (family Magnoliaceae), Glycyrrhizae radix et rhizoma (family Fabaceae), Ginseng radix et rhizoma (family Araliaceae), and Aucklandiae radix (family Asteraceae), and found that herbs are more effective when used in combination. Therefore, it is feasible to establish some methods to study herb pairs comprehensively from different perspectives. This paper aims to provide the latest and most comprehensive information on the six herb pairs and summarize the pattern of CR compatibility effects. It aims to attract more attention, and further experimental studies will be conducted to investigate and evaluate the effects of herb pairs containing CR. These data can also provide valuable references for researchers and also provide more possibilities for future applications in clinical practice and new drug development.

Colorectal cancer is the third most common type of cancer worldwide and has become one of the major human disease burdens. In clinical practice, the treatment of colorectal cancer has been closely related to the use of irinotecan. Irinotecan combines with many other anticancer drugs and has a broader range of drug combinations. Combination therapy is one of the most important means of improving anti-tumor efficacy and overcoming drug resistance. Reasonable combination therapy can lead to better patient treatment options, and inappropriate combination therapy will increase patient risk. For the colorectal therapeutic field, the significance of combination therapy is to improve the efficacy, reduce the adverse effects, and improve the ease of treatment. Therefore, we explored the clinical advantages of its combination therapy based on mechanism or metabolism and reviewed the rationale basis and its limitations in conducting exploratory clinical trials on irinotecan combination therapy, including the results of clinical trials on the combination potentiation of cytotoxic drugs, targeted agents, and herbal medicine. We hope that these can evoke more efforts to conduct irinotecan in the laboratory for further studies and evaluations, as well as the possibility of more in-depth development in future clinical trials.

Abstract Background Traditional Chinese medicine (TCM) has been used to treat various diseases for thousands of years. However, the uncertainty of dosage as well as the lack of systemic evaluation of pharmacology and toxicology is one major reason why TCM remains mysterious and is not accepted worldwide. Hence, we aimed to propose an integrated dose–response metabolomics strategy based on both therapeutic effects and adverse reactions to guide the TCM dosage in treatment. Methods The proposed methodology of integrated dose–response metabolomics includes four steps: dose design, multiple comparison of metabolic features, response calculation and dose–response curve fitting. By comparing the changes of all metabolites under different doses and calculating these changes through superposition, it is possible to characterize the global disturbance and thus describe the overall effect and toxicity of TCM induced by different doses. Rhubarb, commonly used for constipation treatment, was selected as a representative TCM. Results This developed strategy was successfully applied to rhubarb. The dose–response curves clearly showed the efficacy and adverse reactions of rhubarb at different doses. The rhubarb dose of 0.69 g/kg (corresponding to 7.66 g in clinic) was selected as the optimal dose because it was 90% of the effective dose and three adverse reactions were acceptable in this case. Conclusion An integrated dose–response metabolomics strategy reflecting both therapeutic effects and adverse reactions was established for the first time, which we believe is helpful to uncover the mysterious veil of TCM dosage. In addition, this strategy benefits the modernization and internationalization of TCM, and broadens the application of metabolomics.

GRAPHICAL ABSTRACT

Neuropathic pain (NP) affects 7%–10% of the general population and is still hard to cure. Here, we validated the therapeutic effect and demonstrated the mechanism of paeoniflorin and liquiritin combination (PL) on NP from the perspective of integrated lipidomics and transcriptomics for the first time. SwissTargetPrediction indicated that PL mainly targets lipid metabolism. Notably, lipidomics revealed that imbalanced lipid levels in the NP model could be reprogrammed to normal levels by PL treatment. RNA-sequencing showed that PL treatment could also rebalance the lipid metabolism in an indirect manner. Pathway analysis highly enriched the calcium signaling pathway among the most significant categories. Altogether, these findings suggested that PL can not only balance the lipid metabolism in direct and indirect manners but also reverse the dysfunctional activation of the calcium signaling pathway, thereby alleviating NP. This helps to better understand the mechanisms of NP and provides a new important potential therapeutic option for NP.

Unintended pregnancy is a situation that every woman may encounter, and medical abortion is the first choice for women, but abortion often brings many sequelae. Angelica sinensis Radix (Danggui) and Leonuri Herba (Yimucao) are widely used in the treatment of gynecological diseases, which can regulate menstrual disorders, amenorrhea, dysmenorrhea, and promote blood circulation and remove blood stasis, but the mechanism for the treatment of abortion is not clear. We determined the ability of Danggui and Yimucao herb pair (DY) to regulate the Th1/Th2 paradigm by detecting the level of progesterone in the serum and the expression of T-bet and GATA-3 in the spleen and uterus. Then, we detected the level of metabolites in the serum and enriched multiple metabolic pathways. The arachidonic acid pathway can directly regulate the differentiation of Th1/Th2 cells. This may be one of the potential mechanisms of DY in the treatment of abortion.

The central nervous system (CNS) is a vital part of the human nervous system, and the incidence of CNS disease is increasing year by year, which has become a major public health problem and a prominent social problem. At present, the drugs most commonly used in the clinic are receptor regulators, and neurotransmitter inhibitors, but they are accompanied by serious side effects. Therefore, the identification of new drugs and treatment strategies for CNS disease has been a research hotspot in the medical field. Celastrol, a highly bio-active pentacyclic triterpenoid isolated from Tripterygium wilfordii Hook. F, has been proved to have a wide range of pharmacological effects, such as anti-inflammation, immunosuppression, anti-obesity and anti-tumor activity. However, due to its poor water solubility, low bioavailability and toxicity, the clinical development and trials of celastrol have been postponed. However, in recent years, the extensive medical value of celastrol in the treatment of CNS diseases such as nervous system tumors, Alzheimer's disease, Parkinson's disease, cerebral ischemia, multiple sclerosis, spinal cord injury, and amyotrophic lateral sclerosis has gradually attracted intensive attention worldwide. In particular, celastrol has non-negligible anti-tumor efficacy, and as there are no 100% effective anti-tumor drugs, the study of its structural modification to obtain better leading compounds with higher efficiency and lower toxicity has aroused strong interest in pharmaceutical chemists. In this review, research progress on celastrol in CNS diseases and the synthesis of celastrol-type triterpenoid analogues and their application evaluation in disease models, such as CNS diseases and autotoxicity-related target organ cancers in the past decade are summarized in detail, in order to provide reference for future better application in the treatment of CNS diseases.

Chronic constipation is a common gastrointestinal disorder, with a worldwide incidence of 14–30%. It negatively affects quality of life and is associated with a considerable economic burden. As a disease with multiple etiologies and risk factors, it is important to understand the pathophysiology of chronic constipation. The purpose of this review is to discuss latest findings on the roles of gut motility, fluid, and electrolyte transport that contribute to chronic constipation, and the main drugs available for treating patients. We conducted searches on PubMed and Google Scholar up to 9 February 2021. MeSH keywords “constipation”, “gastrointestinal motility”, “peristalsis”, “electrolytes”, “fluid”, “aquaporins”, and “medicine” were included. The reference lists of searched articles were reviewed to identify further eligible articles. Studies focusing on opioid-induced constipation, evaluation, and clinic management of constipation were excluded. The occurrence of constipation is inherently connected to disorders of gut motility as well as fluid and electrolyte transport, which involve the nervous system, endocrine signaling, the gastrointestinal microbiota, ion channels, and aquaporins. The mechanisms of action and application of the main drugs are summarized; a better understanding of ion channels and aquaporins may be helpful for new drug development. This review aims to provide a scientific basis that can guide future research on the etiology and treatment of constipation.

The incidence rate of cardio-cerebrovascular diseases (CCVDs) is increasing worldwide, causing an increasingly serious public health burden. The pursuit of new promising treatment options is thus becoming a pressing issue. Hydroxysafflor yellow A (HSYA) is one of the main active quinochalcone C-glycosides in the florets of Carthamus tinctorius L., a medical and edible dual-purpose plant. HSYA has attracted much interest for its pharmacological actions in treating and/or managing CCVDs, such as myocardial and cerebral ischemia, hypertension, atherosclerosis, vascular dementia, and traumatic brain injury, in massive preclinical studies. In this review, we briefly summarized the mode and mechanism of action of HSYA on CCVDs based on these preclinical studies. The therapeutic effects of HSYA against CCVDs were presumed to reside mostly in its antioxidant, anti-inflammatory, and neuroprotective roles by acting on complex signaling pathways.

Since the outbreak, COVID-19 has spread rapidly across the globe due to its high infectivity and lethality. Age appears to be one of the key factors influencing the status and progression of SARS-CoV-2 infection, as multiple reports indicated that the majority of COVID-19 infections and severe cases are elderly. Most people simply assume that the elderly are more susceptible to SARS-CoV-2 than the young, but the mechanism behind it is still open to question. The older and younger people are at similar risk of infection because their infection process is the same and they must be exposed to the virus first. However, whether they will get sick after exposure to the virus and how their disease progresses depend on their immune mechanisms. In older populations, inflammation and immune aging reduce their ability to resist SARS-CoV-2 infection. Meanwhile, under the influence of comorbidities, ACE2 receptor and various cytokines undergo corresponding changes, thus accelerating the entry, replication, and transmission of SARS-CoV-2 in the body, promoting disease progression, and leading to severe illness and even death. In addition, the relatively fragile mental state of the elderly can also affect their timely recovery from COVID-19. Therefore, once older people are infected with SARS-CoV-2, they are more prone to severe illness and death with a poor prognosis, and they should strengthen protection to avoid exposure to the virus. [ABSTRACT FROM AUTHOR]

Angelica sinensis Radix (ASR), one of the most commonly used traditional Chinese medicines, contains many chemical components such as polysaccharides, volatile oil, flavonoids, amino acids, and organic acids, among which polysaccharides play an indispensable role in the therapeutic effect of ASR. A. sinensis polysaccharide (ASP) has many biological activities, for instance, hematopoietic, anti-tumor, and liver protection, which are closely related to the treatment of human diseases such as chronic anemia, leukemia, and diabetes. In addition, there are excellent application prospects for drug delivery in nanoparticles. This paper reviews the chemical compositions, extraction methods, biological activity, action mechanism, potential clinical applications, nanoparticles, and research prospect of ASP from 2010 to 2020, so as to provide references for its further development. [ABSTRACT FROM AUTHOR]