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Background. Continuous efforts from scientists of diverse fields are necessary not only to better understand the mechanism by which multidrug-resistant (MDR) cancer cells occur, but also to boost the discovery of new cytotoxic compounds to fight MDR phenotypes. Objectives. The present review reports on the contribution of African flora in the discovery of potential cytotoxic phytochemicals against MDR cancer cells. Methodology. Scientific databases such as PubMed, ScienceDirect, Scopus, Google Scholar, and Web of Knowledge were used to retrieve publications related to African plants, isolated compounds, and drug resistant cancer cells. The data were analyzed to highlight cytotoxicity and the modes of actions of extracts and compounds of the most prominent African plants. Also, thresholds and cutoff points for the cytotoxicity and modes of action of phytochemicals have been provided. Results. Most published data related to the antiproliferative potential of African medicinal plants were from Cameroon, Egypt, Nigeria, or Madagascar. The cytotoxicity of phenolic compounds isolated in African plants was generally much better documented than that of terpenoids and alkaloids. Conclusion. African flora represents an enormous resource for novel cytotoxic compounds. To unravel the full potential, efforts should be strengthened throughout the continent, to meet the challenge of a successful fight against MDR cancers.

The reductionist concept, based on the ligand–receptor interaction, is not a suitable model for adaptogens, and herbal preparations affect multiple physiological functions, revealing polyvalent pharmacological activities, and are traditionally used in many conditions. This review, for the first time, provides a rationale for the pleiotropic therapeutic efficacy of adaptogens based on evidence from recent gene expression studies in target cells and where the network pharmacology and systems biology approaches were applied. The specific molecular targets and adaptive stress response signaling mechanisms involved in nonspecific modes of action of adaptogens are identified.

Tumor heterogeneity has been compared with Darwinian evolution and survival of the fittest. The evolutionary ecosystem of tumors consisting of heterogeneous tumor cell populations represents a considerable challenge to tumor therapy, since all genetically and phenotypically different subpopulations have to be efficiently killed by therapy. Otherwise, even small surviving subpopulations may cause repopulation and refractory tumors. Single-cell sequencing allows for a better understanding of the genomic principles of tumor heterogeneity and represents the basis for more successful tumor treatments. The isolation and sequencing of single tumor cells still represents a considerable technical challenge and consists of three major steps: (1) single cell isolation (e.g., by laser-capture microdissection), fluorescence-activated cell sorting, micromanipulation, whole genome amplification (e.g., with the help of Phi29 DNA polymerase), and transcriptome-wide next generation sequencing technologies (e.g., 454 pyrosequencing, Illumina sequencing, and other systems). Data demonstrating the feasibility of single-cell sequencing for monitoring the emergence of drug-resistant cell clones in patient samples are discussed herein. It is envisioned that single-cell sequencing will be a valuable asset to assist the design of regimens for personalized tumor therapies based on tumor subpopulation-specific genetic alterations in individual patients.

Post-traumatic stress disorder (PTSD) widely occurs among victims or witness of disasters. With flashbacks, hyperarousal, and avoidance being the typical symptoms, PTSD became a focus of psychological research. The earthquake in Wenchuan, China, on May 12, 2008, was without precedent in magnitude and aftermath and caused huge damage, which drew scientists’ attention to mental health of the survivors. We conducted a systematic overview by collecting published articles from the PubMed database and classifying them into five points: epidemiology, neuropathology, biochemistry, genetics and epigenetics, and treatment. The large body of research during the past 6 years showed that adolescents and adults were among the most studied populations with high prevalence rates for PTSD. Genomic and transcriptomic studies focusing on gene × environment studies as well as epigenetics are still rare, although a few available data showed great potential to better understand the pathophysiology of PTSD as multifactorial disease. Phytotherapy with Chinese herbs and acupuncture are rarely reported as of yet, although the first published data indicated promising therapy effects. Future studies should focus on the following points: (1) The affected populations under observation should be better defined concerning individual risk factor, time of observation, spatial movement, and individual disease courses of patients. (2) The role of social support for prevalence rates of PTSD should be observed in more detail. (3) Efficacy and safety of Chinese medicine should be studied to find potential interventions and effective treatments of PTSD.

Acupuncture is widely used around the whole world nowadays and exhibits significant efficacy against many chronic diseases, especially in pain-related diseases. With the rapid development of artificial intelligence (AI), its implementation into acupuncture has achieved a series of significant breakthroughs in many areas of acupuncture practice, such as acupoints selection and prescription, acupuncture manipulation identification, acupuncture efficacy prediction, and so on. The paper will discuss the significant theoretical and technical achievements in AI-directed acupuncture. AI-based data mining methods uncovered crucial acupoint combinations for treating various diseases, which provide a scientific basis for acupoints prescription in clinical practice. Furthermore, the rapid development of modern TCM instruments facilitates the integration of modern medical instruments, AI techniques, and acupuncture. This integration significantly improves the quantification, objectification, and standardization of acupuncture as well as the delivery of clinical personalized acupuncture therapy. Machine learning-based clinical efficacy prediction of acupuncture can help doctors screen patients who may benefit from acupuncture treatment. However, the existing challenges require additional work for developing AI-directed acupuncture. Some include a better understanding of ancient Chinese philosophy for AI researchers, TCM acupuncture theory-based explanation of the knowledge discoveries, construction of acupuncture databases, and clinical trials for novel knowledge validation. This review aims to summarize the major contribution of AI techniques to the discovery of novel acupuncture knowledge, the improvement for acupuncture safety and efficacy, the development and inheritance of acupuncture, and the major challenges for the further development of AI-directed acupuncture. The development of acupuncture can progress with the help of AI.

The complexity of our life experiences and the rapid progress in science and technology clearly necessitate reflections from the humanities. The ever-growing intersection between science and society fosters the emergence of novel interdisciplinary fields of research. During the past decade, Medical Humanities arose to meet the need to unravel hidden information beyond technology-driven and fact-based medicine. In the present paper, we put forward the hypothesis that there is a similar requirement to develop Pharmaceutical Humanities as an academic discipline within pharmacy and pharmaceutical biology. Based on Thomas Kuhn’s epistemological theory on the structure of scientific revolutions, one may argue that a paradigm change for Pharmaceutical Humanities might open new levels of insight. Many complex diseases (e.g., cancer, neurological diseases, and mental disorders) remain uncurable for many patients by current pharmacotherapies, and the old beaten paths in our therapeutic thinking may at least partly have to be left behind. By taking examples from Pharmaceutical Biology, we attempt to illustrate that the transdisciplinary dialogue with the humanities is fertile ground not only for enlarging our understanding of disease-related conditions but also for exploring new ways of combatting diseases. In this context, we discuss aspects related to traditional herbal medicine, fair access and benefit sharing of indigenous knowledge about medicinal plants, post-traumatic stress syndrome, the opioid crisis, stress myocardiopathy (broken heart syndrome), and global environmental pollution with microplastics. We also explore possibilities for a narrative turn in pharmacy. The urgent need for inter- and transdisciplinary solutions to pressing health-related problems in our society may create a scholarly atmosphere for the establishment of Pharmaceutical Humanities as a fruitful terrain to respond to the current demands of both science and society.

Cancer is one of the major problems affecting public health worldwide. As other cultures, the populations of the Near East rely on medicinal herbs and their preparations to fight cancer. We compiled data derived from historical ethnopharmacological information as well as and results and clinical findings extracted from different literature databases including (PubMed, Scopus, Web of Science, and Google Scholar) during the past two decades. In this survey, we analyzed the huge amount of data available on anticancer ethnopharmacological sources used in the Near East. Medicinal herbs are the most dominant ethnopharmacological formula used among cancer's patients in the Near East. The data obtained highlight for the first time the most commonly used medicinal plants in the Near East area for cancer treatment illustrating their importance as natural anticancer agents. The literature survey reveals that various species, various species, , , , , various species, , and others belong to the most frequently used plants among cancer patients in the Near East countries. Molecular modes of action that have been investigated for plant extracts and isolated compounds from Near East include cell cycle arrest and apoptosis induction with participation of major player in these processes such as p53 and p21, Bcl-2, Bax, cytochrome release, poly (ADP-ribose) polymerase cleavage, activation of caspases, etc. The ethnopharmacology of the Near East was influenced by Arabic and Islamic medicine and might be promising for developing new natural and safe anticancer agents. Further research is required to elucidate their cellular and molecular mechanisms and to estimate their clinical activity.

Background: Despite some evidence supporting the synergy concept, the commonly known assumption that combinations of several herbs in one formulation can have better efficacy due to additive or synergistic effects has yet to be unambiguously and explicitly studied. Study aim: The study aimed to reveal the molecular interactions in situ of host cells in response to botanical hybrid preparations (BHP) intervention and justify the benefits of implementing BHP in clinical practice. Results: This prospective literature review provides the results of recent clinical and network pharmacology studies of BHP of Rhodiola rosea L. (Arctic root) with other plants, including Withania somnifera (L.) Dunal (ashwagandha), (Camellia sinensis (L.) Kuntze (green tea), Eleutherococcus senticosus (Rupr. and Maxim.) Maxim. (eleuthero), Schisandra chinensis (Turcz.) Baill. (schisandra), Leuzea carthamoides (Willd.) DC., caffeine, Cordyceps militaris L., Ginkgo biloba L.(ginkgo), Actaea racemosa L. (black cohosh), Crocus sativus L. (saffron), and L-carnosine. Conclusions: The most important finding from network pharmacology studies of BHP was the evidence supporting the synergistic interaction of BHP ingredients, revealing unexpected new pharmacological activities unique and specific to the new BHP. Some studies show the superior efficacy of BHP compared to mono-drugs. At the same time, some a priori-designed combinations can fail, presumably due to antagonistic interactions and crosstalk between molecular targets within the molecular networks involved in the cellular and overall response of organisms to the intervention. Network pharmacology studies help predict the results of studies aimed at discovering new indications and unpredicted adverse events.

The main protease (Mpro or 3CLpro) in coronaviruses represents a promising specific drug target as it is essential for the cleavage of the virus polypeptide and has a unique cleavage site that does not exist in human host proteases. In this study, we explored potential natural pan-coronavirus drugs using in vitro and in silico approaches and three coronavirus main proteases as treatment targets. The PyRx program was used to screen 39,442 natural-product-like compounds from the ZINC database and 121 preselected phytochemicals from medicinal plants with known antiviral activity. After assessment with Lipinski’s rule of five, molecular docking was performed for the top 33 compounds of both libraries. Enzymatic assays were applied for the top candidates from both in silico approaches to test their ability to inhibit SARS-CoV-2 Mpro. The four compounds (hypericin, rosmarinic acid, isorhamnetin, and luteolin) that most efficiently inhibited SARS-CoV-2 Mpro in vitro were further tested for their efficacy in inhibiting Mpro of SARS-CoV-1 and MERS-CoV. Microscale thermophoresis was performed to determine dissociation constant (Kd) values to validate the binding of these active compounds to recombinant Mpro proteins of SARS-CoV-2, SARS-CoV-1, and MERS-CoV. The cytotoxicity of hypericin, rosmarinic acid, isorhamnetin, and luteolin was assessed in human diploid MRC-5 lung fibroblasts using the resazurin cell viability assay to determine their therapeutic indices. Sequence alignment of Mpro of SARS-CoV-2 demonstrated 96.08%, 50.83%, 49.17%, 48.51%, 44.04%, and 41.06% similarity to Mpro of other human-pathogenic coronaviruses (SARS-CoV-1, MERS-CoV, HCoV-NL63, HCoV-OC43, HCoV-HKU1, and HCoV-229E, respectively). Molecular docking showed that 12 out of 121 compounds were bound to SARS-CoV-2 Mpro at the same binding site as the control inhibitor, GC376. Enzyme inhibition assays revealed that hypericin, rosmarinic acid, isorhamnetin, and luteolin inhibited Mpro of SARS-CoV-2, while hypericin and isorhamnetin inhibited Mpro of SARS-CoV-1; hypericin showed inhibitory effects toward Mpro of MERS-CoV. Microscale thermophoresis confirmed the binding of these compounds to Mpro with high affinity. Resazurin assays showed that rosmarinic acid and luteolin were not cytotoxic toward MRC-5 cells, whereas hypericin and isorhamnetin were slightly cytotoxic. We demonstrated that hypericin represents a potential novel pan-anti-coronaviral agent by binding to and inhibiting Mpro of several human-pathogenic coronaviruses. Moreover, isorhamnetin showed inhibitory effects toward SARS-CoV-2 and SARS-CoV-1 Mpro, indicating that this compound may have some pan-coronaviral potential. Luteolin had inhibitory effects against SARS-CoV-2 Mpro.

Background Drug-induced liver injury (DILI) is gradually becoming a common global problem that causes acute liver failure, especially in acute hepatic damage caused by acetaminophen (APAP). Paeoniflorin (PF) has a wide range of therapeutic effects to alleviate a variety of hepatic diseases. However, the relationship between them is still poorly investigated in current studies. Purpose This work aimed to explore the protective effects of PF on APAP-induced hepatic damage and researched the potential molecular mechanisms. Methods C57BL/6J male mice were injected with APAP to establish DILI model and were given PF for five consecutive days for treatment. Aiming to clarify the pharmacological effects, the molecular mechanisms of PF in APAP-induced DILI was elucidated by high-throughput and other techniques. Results The results demonstrated that serum levels of ALP, γ-GT, AST, TBIL, and ALT were decreased in APAP mice by the preventive effects of PF. Moreover, PF notably alleviated hepatic tissue inflammation and edema. Meanwhile, the results of TUNEL staining and related apoptotic factors coincided with the results of transcriptomics, suggesting that PF inhibited hepatocyte apoptosis by regulated MAPK signaling. Besides, PF also acted on reactive oxygen species (ROS) to regulate the oxidative stress for recovery the damaged mitochondria. More importantly, transmission electron microscopy showed the generation of autophagosomes after PF treatment, and PF was also downregulated mTOR and upregulated the expression of autophagy markers such as ATG5 , ATG7 , and BECN1 at the mRNA level and LC3, p62, ATG5, and ATG7 at the protein level, implying that the process by which PF exerted its effects was accompanied by the occurrence of autophagy. In addition, combinined with molecular dynamics simulations and western blotting of MAPK, the results suggested p38 as a direct target for PF on APAP. Specifically, PF-activated autophagy through the downregulation of MAPK/mTOR signaling, which in turn reduced APAP injury. Conclusions Paeoniflorin mitigated liver injury by activating autophagy to suppress oxidative stress and apoptosis via the MAPK/mTOR signaling pathway. Taken together, our findings elucidate the role and mechanism of paeoniflorin in DILI, which is expected to provide a new therapeutic strategy for the development of paeoniflorin. Graphical abstract