Enzyme Activity of Natural Products on Cytochrome P450

Drug-metabolizing enzymes, particularly the cytochrome P450 (CYP450) monooxygenases, play a pivotal role in pharmacokinetics. CYP450 enzymes can be affected by various xenobiotic substrates, which will eventually be responsible for most metabolism-based herb–herb or herb–drug interactions, usually involving competition with another drug for the same enzyme binding site. Compounds from herbal or natural products are involved in many scenarios in the context of such interactions. These interactions are decisive both in drug discovery regarding the synergistic effects, and drug application regarding unwanted side effects. Herein, this review was conducted as a comprehensive compilation of the effects of herbal ingredients on CYP450 enzymes. Nearly 500 publications reporting botanicals’ effects on CYP450s were collected and analyzed. The countries focusing on this topic were summarized, the identified herbal ingredients affecting enzyme activity of CYP450s, as well as methods identifying the inhibitory/inducing effects were reviewed. Inhibitory effects of botanicals on CYP450 enzymes may contribute to synergistic effects, such as herbal formulae/prescriptions, or lead to therapeutic failure, or even increase concentrations of conventional medicines causing serious adverse events. Conducting this review may help in metabolism-based drug combination discovery, and in the evaluation of the safety profile of natural products used therapeutically.

REVIEW ON NASA ROGA (NASAL DISEASES) IN AYURVEDA MEDICINE WITH SPECIAL REFERENCE TO THE PINASA (CATARRH) IN SRI LANKAN TRADITIONAL MEDICINE

Pinasa (Catarrh) is an inflammatory disease of respiratory mucosa accompanied by sneezing, cough, headache, rhinorrhea, itching in throat and eyes. This cascade challenges the management of the disease and ultimately leads to negative impact to quality of life of the patient. At present, intervention strategies have been implemented in the management based on the herbal formulae with the light of Sri Lankan traditional medicine (SLTM). The study is focused to compile this scattered indigenous knowledge on Pinasa and compare them with the findings of Ayurveda medicine to explore the diagnosis and management gaps in both Ayurveda and SLTM. Data collection was done through documentary surveys, interviews and observations. The study revealed that the Pinasa has been considered as collective phenomena of Pratishyaya, Dushta Pratishyaya and Apinasa in Ayurveda medicine. Similarities has been found in etiology, clinical features and treatments stratergies in SLTM and Ayurveda medicine but types of the disease are varying. Pinasa was classified into 12 and 19 sub types in SLTM while 05 sub types of Pratishyaya have been described in Ayurveda medicine. Snehana (oleation), Swedana (fomentation) and Nasya (inhalation) were mentioned as external treatment modalities in Ayurveda medicine while same regimn are mentioned in SLTM but in different medical terminologies. Decoctions, pills, Kalka, Choorna and porridge were administered as internal remedies in both the medical system with different formulae while Nidana Parivarjana and Patyapatya Sewana considered as preventive measures. It can be concluded that the knowledge on Pinasa in SLTM is crucial important to conduct further research studies to find effective management along with novel preparation for Pinasa.

Natural Products from Medicinal Plants with Anti-Human Coronavirus Activities

Since the emergence of severe acute respiratory syndrome caused by coronavirus 2 (SARS-CoV-2) first reported in Wuhan, China in December 2019, COVID-19 has spread to all the continents at an unprecedented pace. This pandemic has caused not only hundreds of thousands of mortalities but also a huge economic setback throughout the world. Therefore, the scientific communities around the world have focused on finding antiviral therapeutic agents to either fight or halt the spread of SARS-CoV-2. Since certain medicinal plants and herbal formulae have proved to be effective in treatment of similar viral infections such as those caused by SARS and Ebola, scientists have paid more attention to natural products for effective treatment of this devastating pandemic. This review summarizes studies and ethnobotanical information on plants and their constituents used for treatment of infections caused by viruses related to the coronavirus family. Herein, we provide a critical analysis of previous reports and how to exploit published data for the discovery of novel therapeutic leads to fight against COVID-19.

Deciphering the Pharmacological Mechanisms of Guizhi-Fuling Capsule on Primary Dysmenorrhea Through Network Pharmacology

Guizhi-Fuling capsule (GZFLC), originated from a classical traditional Chinese herbal formula Guizhi-Fuling Wan, has been clinically used for primary dysmenorrhea in China. Nonetheless, the underlying pharmacological mechanisms of GZFLC remain unclear. The integration of computational and experimental methods of network pharmacology might be a promising way to decipher the mechanisms. In this study, the target profiles of 51 representative compounds of GZFLC were first predicted by a high-accuracy algorithm, drugCIPHER-CS, and the network target of GZFLC was identified. Then, potential functional modules of GZFLC on primary dysmenorrhea were investigated using functional enrichment analysis. Potential bioactive compounds were recognized by hierarchical clustering analysis of GZFLC compounds and first-line anti-dysmenorrhea drugs. Furthermore, the potential anti-dysmenorrhea mechanisms of GZFLC were verified through enzyme activity assays and immunofluorescence tests. Moreover, effects of GZFLC on primary dysmenorrhea were evaluated in oxytocin-induced dysmenorrhea murine model. In the network target analysis, GZFLC may act on five functional modules of pain, inflammation, endocrine, blood circulation and energy metabolism. Integrating computational and experimental approaches, we found that GZFLC significantly inhibited the writhing response and reduced the degree of uterine lesions in oxytocin-induced dysmenorrhea murine model. Furthermore, GZFLC may partially alleviate primary dysmenorrhea by inhibiting cyclooxygenase 2 (COX2) and downregulating MAPK signaling pathway. Consequently, GZFLC presented pain relief and sustained benefits for primary dysmenorrhea. This study could provide a scientific approach for deciphering pharmacological mechanisms of herbal formulae through network pharmacology.

Analysis of Chinese herbal formulae recommended for COVID-19 in different schemes in China: A data mining Approach

Background: Novel coronavirus pneumonia (NCP), or coronavirus disease 2019 (COVID-19), is a worldwide health threat that has affected millions of people globally. Traditional Chinese medicine (TCM) has been introduced for the treatment of COVID-19. However, efficacy differs among herbal medicines, and the ideal prescription pattern for TCM herbal formulae for COVID-19 treatment needs to be explored. Therefore, the data mining method has been used in this study to analyze the TCM prescription pattern for COVID-19. Objective: The aim of this study was to analyze the TCM prescription pattern in Regional Schemes in China for COVID-19 in order to provide a new reference for the use of TCM in COVID-19 treatment. Method: By searching the TCM treatment protocols of COVID-19 in 23 Regional Schemes, TCM syndromes and herbal medicines were analyzed by data mining. The Ancient and Modern Medical Case Cloud Platform (V2.1 personal Edition) was used to perform frequency statistics, correlation analysis, and cluster analysis. A total of 82 TCM syndromes and 171 Chinese herbal medicines were found. The course of the disease can be divided into the early stage, middle stage, severe stage, and recovery stage. Results: In the early stage, the focus is primarily on resolving dampness, dispelling cold, and diffusing the lungs. In the middle stage, the treatment priority is clearing heat and resolving toxins, promoting lung function, and relieving asthma. In the severe stage, the focus is on tonifying Qi, restoring Yang, and relieving depletion of Yin and Yang. In the recovery stage, the main treatment is to invigorate the spleen and regulate Qi, tonify Qi, nourish Yin, and clear residual disease evil. There are certain differences between the Regional Schemes and the Nation Schemes, but the core prescription pattern of the former is consistent with the latter. The effectiveness of these 171 Chinese herbs include but are not limited to inhibiting COVID-19, strengthening immune system function, preventing heart failure, acting as antioxidants, oxidative stress inhibitory effects, maintaining organ function, and improving leukocyte survival. Conclusion: This study may help to improve understanding of TCM herbal prescription pattern, practices, reveal the efficacy of combinations of Chinese herbs, and provide new ideas for TCM treatment for COVID-19.