Microbiological acceptance criteria, specifications of herbal drugs and herbal drug preparations in various pharmacopoeias: a global scenario.

PURPOSE: A pharmacopoeia is a compendium of guidelines and criteria for drug quality. It was established by a national or regional entity and has legal significance. This applies to administration of drugs in a particular nation or region. METHOD: In this study, the differences and similarities of microbiological acceptance criteria, specifications for microbial enumeration of herbal drugs and herbal drug preparations in 14 national and international pharmacopeias were investigated. RESULTS: It was found that 12 pharmacopeias have given separate microbial limits for total aerobic microbial count (TAMC) and total yeast and mold count (TYMC), and a list of specified microorganisms for which acceptance criteria are defined. However, similarities were noticed in Ph.Eur, Ph. Helv and, BP. Salmonella, and Escherichia coli are the most common pathogens specified for herbal preparations in which boiling water is added prior to use and for internal use in all Pharmacopoeias because they serve as indicators of potential contamination. CONCLUSION: From this study, it can be concluded that the differences in microbial limit tests and their acceptance criteria as specified in the various pharmacopoeias need to be harmonized. It will become a more convenient option for global drug manufacturers to import/export herbal drugs, and this would also eliminate the burden of performing various analytical methods and comply with different microbial acceptance criteria set by various pharmacopoeias. The comparative data obtained from this study will be used to develop strategies for revisions of pharmacopoeias in a harmonized manner with respect to microbiological acceptance criteria, specifications for microbial enumeration of herbal drugs and herbal drug preparations.

Resultant compound from sublimation test for Gentianae Radix in Japanese Pharmacopoeia was 5-(hydroxymethyl)furfural.

Gentianae Radix, an herbal medicine, has been used as a gastrointestinal drug in Japan. In the Japanese Pharmacopoeia 18th Revision, the sublimation test is specified as an identification test for Gentianae Radix. The compound obtained in this sublimation test was believed to be gentisin, a xanthone family compound. However, the compound we identified using liquid chromatography-high-resolution mass spectrometry (LC-HRMS) and 1H- and 13C-NMR was 5-(hydroxymethyl)furfural (5-HMF). The same compound was found to be a sublimate of Gentianae Scabrae Radix and Gentianae Macrophyllae Radix, belonging to the same genus as Gentianae Radix. These results indicate the necessity to revise the identification test for Gentianae Radix to a more unique method.

The Role of Traditional Chinese Medicine and Chinese Pharmacopoeia in the Evaluation and Treatment of COVID-19.

The epidemic prompted by COVID-19 continues to spread, causing a great risk to the general population's safety and health. There are still no drugs capable of curing it. Severe Acute Respiratory Syndrome (SARS) and Middle East Respiratory Syndrome (MERS) are the two other diseases caused by coronaviruses. Traditional Chinese Medicine (TCM) showed benefits in treating SARS and MERS by preventing the disease early, substantially mitigating symptoms, shortening the treatment period, and minimizing risks and adverse reactions caused by hormone therapy. Although several vaccines have been developed and are being used for the treatment of COVID-19, existing vaccines cannot provide complete protection against the virus due to the rapid evolution and mutation of the virus, as mutated viral epitopes evade the vaccine's target and decrease the efficacy of vaccines. Thus, there is a need to develop alternative options. TCM has demonstrated positive effects in the treatment of COVID-19. Previous research studies on TCM showed broad-spectrum antiviral activity, offering a range of possibilities for their potential use against COVID-19. This study shed some light on common TCM used for SARS and MERS outbreaks and their effective use for COVID-19 management. This study provides new insights into COVID-19 drug discovery.

A study on pharmaceutical text relationship extraction based on heterogeneous graph neural networks.

Effective information extraction of pharmaceutical texts is of great significance for clinical research. The ancient Chinese medicine text has streamlined sentences and complex semantic relationships, and the textual relationships may exist between heterogeneous entities. The current mainstream relationship extraction model does not take into account the associations between entities and relationships when extracting, resulting in insufficient semantic information to form an effective structured representation. In this paper, we propose a heterogeneous graph neural network relationship extraction model adapted to traditional Chinese medicine (TCM) text. First, the given sentence and predefined relationships are embedded by bidirectional encoder representation from transformers (BERT fine-tuned) word embedding as model input. Second, a heterogeneous graph network is constructed to associate words, phrases, and relationship nodes to obtain the hidden layer representation. Then, in the decoding stage, two-stage subject-object entity identification method is adopted, and the identifier adopts a binary classifier to locate the start and end positions of the TCM entities, identifying all the subject-object entities in the sentence, and finally forming the TCM entity relationship group. Through the experiments on the TCM relationship extraction dataset, the results show that the precision value of the heterogeneous graph neural network embedded with BERT is 86.99% and the F1 value reaches 87.40%, which is improved by 8.83% and 10.21% compared with the relationship extraction models CNN, Bert-CNN, and Graph LSTM.

Avicenna's pharmacopeia for the treatment of animal bites.

Envenomation is a common medical problem. The Canon of Medicine written by Avicenna is one of the reliable sources of Persian medicine. The present study aims to identify Avicenna's clinical pharmacology approach and the pharmacopeia used for the treatment of animal envenomations and also to evaluate the related data in light of the current medicine. The Canon of Medicine was searched using related Arabic keywords for the contents about the treatment of animal bites. A literature search was conducted in scientific databases including PubMed, Scopus, Google Scholar, and Web of Science to obtain relevant data. Avicenna recommended one hundred and eleven medicinal plants for the treatment of bites of vertebrate and invertebrate venomous animals including snakes, scorpions, spiders, wasps, and centipedes. He mentioned different methods of administrating these drugs including oral drugs, lotions, sprayed drugs, slow-dissolving tablets in the mouth, and enemas. Moreover, he paid special attention to pain relief in addition to specific treatments for animal bites. In the Canon of Medicine, Avicenna recommended several medicinal plants alongside analgesics for the management and treatment of animal envenomations. The current research elucidates the clinical pharmacology and pharmacopeia of Avicenna for the treatment of animal envenomations. Further research is encouraged to evaluate the efficacy of these therapeutic agents for the treatment of animal bites.

[Analysis and suggestions on harvest period standards of plant medicinal materials in 2020 edition of Chinese Pharmacopoeia].

The improvement of the harvest period standards is critical in the quality control of Chinese medicinal materials. The present study statistically analyzed the harvest period standards of plant medicinal materials in the 2020 edition of Chinese Pharmacopoeia(Vol.Ⅰ) and put forward the existing problems and suggestions based on herbal records and modern research to provide references for the improvement of the standards. According to the statistical analysis, in 499 types of plant medicinal materials, harvest period standards are recorded under 486 types, accounting for 97.4%, and are lacking in the remaining. Only one medicinal material(Stellariae Radix) is recorded with the standard of the harvest year. The standards of the harvest season and phenological period are recorded under 233 types, accounting for 46.7%. For 237 types, only harvest season is specified, accounting for 47.5%, and for 15 types, only harvest phenological period is specified, accounting for 3.0%. Among 222 types mainly derived from cultivation and 51 types from wild resources and cultivation, only 11 types are recorded with harvest period of cultivated products. Only Stellariae Radix is recorded with the harvest period standards for the wild and cultivated products separately. The harvest period standards of plant medicinal materials with different medicinal parts have certain rules to follow. The main problems about the harvest period standards are discovered. Specifically, no harvest period standards are recorded under 13 types of plant medicinal materials. Almost all perennial cultivated medicinal materials are not recorded with harvest year standard. No phenological period standard is found under 250 types of plant medicinal materials. There is no clear distinction between the harvest period standards of cultivated and wild products. The evidence for harvest period standards of 26 types of plant medicinal materials that can be harvested all year round is insufficient. As a result, it is proposed to strengthen basic research in response to the above-mentioned problems and improve the harvest period standards as soon as possible to ensure the quality of Chinese medicinal materials.

Analysis and suggestions on harvest period standards of plant medicinal materials in 2020 edition of Chinese Pharmacopoeia / 中国中药杂志

The improvement of the harvest period standards is critical in the quality control of Chinese medicinal materials. The present study statistically analyzed the harvest period standards of plant medicinal materials in the 2020 edition of Chinese Pharmacopoeia(Vol.Ⅰ) and put forward the existing problems and suggestions based on herbal records and modern research to provide references for the improvement of the standards. According to the statistical analysis, in 499 types of plant medicinal materials, harvest period standards are recorded under 486 types, accounting for 97.4%, and are lacking in the remaining. Only one medicinal material(Stellariae Radix) is recorded with the standard of the harvest year. The standards of the harvest season and phenological period are recorded under 233 types, accounting for 46.7%. For 237 types, only harvest season is specified, accounting for 47.5%, and for 15 types, only harvest phenological period is specified, accounting for 3.0%. Among 222 types mainly derived from cultivation and 51 types from wild resources and cultivation, only 11 types are recorded with harvest period of cultivated products. Only Stellariae Radix is recorded with the harvest period standards for the wild and cultivated products separately. The harvest period standards of plant medicinal materials with different medicinal parts have certain rules to follow. The main problems about the harvest period standards are discovered. Specifically, no harvest period standards are recorded under 13 types of plant medicinal materials. Almost all perennial cultivated medicinal materials are not recorded with harvest year standard. No phenological period standard is found under 250 types of plant medicinal materials. There is no clear distinction between the harvest period standards of cultivated and wild products. The evidence for harvest period standards of 26 types of plant medicinal materials that can be harvested all year round is insufficient. As a result, it is proposed to strengthen basic research in response to the above-mentioned problems and improve the harvest period standards as soon as possible to ensure the quality of Chinese medicinal materials.

[Detection of Residual Solvents in Commercial Supplements Using Headspace (HS)-GC-MS].

In order to understand the actual state of residual solvents contained in commercial supplements, we performed a simultaneous analysis of residual solvents by headspace (HS)-GC-MS with reference to the Japanese Pharmacopoeia's "Residual Solvents", for 29 products selected from among commercial supplements (e.g., revitalizers, weight loss pills) that are deeply colored or contain coating agents and extract powder. As a result, benzene (class 1) was detected in eight black-colored supplements, and hexane (class 2B) was also detected in one of those products. On the other hand, methanol (class 2A) was detected in four products containing coating agents and extract powders, such as citrus peel extract. None of these residual solvents exceeded the concentration limits set by the Japanese Pharmacopoeia. Benzene was detected at 1.7 µg/g, which was near the concentration limit, in some products. As raw materials used for the manufacture of the black-colored supplements from which benzene was detected commonly included activated carbon, we analyzed the residual solvents contained in activated carbon commercially available for use as food additive and in food production and medicine. As a result, benzene was detected at high concentrations in activated carbon made from hemp (approximately 29 µg/g) and bamboo (approximately 140 µg/g).

SuperTCM: A biocultural database combining biological pathways and historical linguistic data of Chinese Materia Medica for drug development.

AIM OF THE STUDY: Botanicals used in Traditional Chinese Medicine (TCM) are a rich source for drug discovery and provide models for multi-component drug development. To facilitate the studies of the actions of TCM drugs and expand their applications, a comprehensive database is urgently required. METHODS: One online resource connects all the relevant data from multiple scientific sources and languages. Drug information from published TCM databases and the official Chinese Pharmacopoeia as well as specialized meta-websites such as Kew's Medicinal Plant Names Service was integrated on a higher level. RESULTS: Our database, SuperTCM, covers the aspects of TCM derived from medicinal plants, encompassing pharmacological recipes up to chemical compounds. It provides the information for 6516 TCM drugs (or "herbs") with 5372 botanical species, 55,772 active ingredients against 543 targets in 254 KEGG pathways associated with 8634 diseases. SuperTCM is freely available at http://tcm.charite.de/supertcm.

Discrepancies in the German Pharmacopoeia procedure for quality control of Quillaja saponin extracts.

This study focused on the evaluation of Quillaja saponin extracts with the additional quality designation DAB-which means the abbreviation of the German Pharmacopoeia (Deutsches Arzneibuch). This label suggests that Quillaja saponin extracts marked in this way are of pharmacopoeial quality and thus stand out from other Quillaja saponin extracts. The DAB ninth edition listed Quillaia saponin as a reagent. According to DAB, its quality must be checked by thin-layer chromatography (TLC), and three closely spaced zones in a defined retention factor (Rf) interval specify the saponin reagent. All the Quillaja saponin extracts obtained from different manufacturers and labeled as DAB quality complied with the TLC test. However, the analysis with high-performance liquid chromatography-quadrupole time-of-flight-mass spectrometry (HPLC-Q-ToF-MS) clearly showed additionally an intense peak pattern of Madhuca saponins in all measured samples. The TLC test for Mahua seed cake, which is the press residue from Madhuca longifolia, surprisingly showed the same three closely spaced zones in the defined Rf interval. The three zones could be identified as Mi-saponins from Madhuca after scraping and extracting them from the stationary phase of the TLC plate and subsequent measurement by HPLC-Q-ToF-MS. Therefore, the specification of the saponin reagent in DAB characterizes erroneously Madhuca saponins that are not listed as a saponin plant source for the saponin reagent.

An investigation of the pharmacological applications used for the Ancient Egyptian systemic model 'ra-ib' compared with modern Traditional Chinese Medicine.

ETHNOPHARMACOLOGICAL RELEVANCE: Ancient Egyptian texts only offer glimpses into their conceptual understandings of the inner-body and illness manifestation. Explanations of how prescribed materia medica were believed to work are rare and obscure, often resulting in modern approximations for ancient terminology such as 'ra-ib'-an ancient Egyptian classification predominantly translated as 'stomach'-leading to misunderstandings of historical texts, and therefore their use of pharmacology. AIM OF THE STUDY: To investigate the ra-ib and the explanatory models of illness from the Egyptian perspective, and to explore the link between these and the prescribed selection of materia medica. To then compare the conceptual mechanics of these treatment strategies with those of another non-Western tradition-namely Traditional Chinese Medicine (TCM)-to provide further insight into potential conceptual frameworks. MATERIALS AND METHODS: We conducted a case study of a unit of Ancient Egyptian texts focusing on the ra-ib. Totalling 34 prescriptions, the first stage lexicographically analysed the texts using cognitive linguistic and translation theories to produce our new understanding. This enabled our comparison of the mechanics of materia medica usage within these texts with those found in TCM outlined by the Pharmacopoeia of the Peoples Republic of Pharmacopeia of the People's Republic of China 2015 for the relevant ingredients. RESULTS: the study demonstrated that-rather than denoting the organ 'stomach'-ra-ib instead constitutes a system running from the mouth, downward to the anus. This is best translated as 'inner thoroughfare', and changes the way in which we attempt to understand potential motivations in the selection of ingredients. By exploring common themes in the use of eleven securely translated ingredients from the Egyptian corpus and the Pharmacopoeia of the People's Republic of China-representing a modern traditional system which understands the body via a series of interconnected systems-we were able to highlight certain themes which might be 'universal' to system-based traditions; this provided new insights into the Egyptian motivations for treatment selection. CONCLUSIONS: Having gained the ancient view of the body and illness, cultural comparisons are important for providing further potential insights and clarifications of a discontinued historical healing tradition. The new understanding of the ra-ib from our study greatly changes the way in which we understand the dynamics of Egyptian ethnopharmacological source material from this period.

Medicinal plants from the 14th edition of the Russian Pharmacopoeia, recent updates.

ETHNOPHARMACOLOGICAL RELEVANCE: Herbal medicine in Russia has a long history starting with handwritten herbalist manuscripts from the Middle Ages to the officinal Pharmacopoeia of the 21st century. The "herbophilious" Russian population has accumulated a lot of knowledge about the beneficial effects of local medicinal plants. Yet, for a long time, Russian traditional and officinal herbal medicine was not well known to the international audience. In our previous comprehensive review, we discussed the pharmacological effects of specific plants included in the 11th edition of the Pharmacopoeia of the USSR, which was also for a while used in Russia. The 14th edition of the Russian Federation's State Pharmacopoeia was implemented in 2018. AIM OF THE REVIEW: The aims of the present review are: (i) to trace the evolution of medicinal plant handling from handwritten herbalist manuscripts to Pharmacopoeias; (ii) to describe the modern situation with regulatory documents for herbal medicinal products and their updated classification; (iii) to summarize and discuss the pharmacology, safety, and clinical data for new plants, which are included in the new edition of the Pharmacopoeia. METHODS: New medicinal plants included in the 14th edition of the Russian Federation's State Pharmacopoeia were selected. We carefully searched the scientific literature for data related to traditional use, pharmacological, clinical application, and safety. The information was collected from local libraries in Saint-Petersburg, the online databases E-library.ru, Scopus, Web of Science, and the search engine Google scholar. RESULTS: Investigating the evolution of all medicinal plants referred to in the Russian Pharmacopoeias led us to the identification of ten medicinal plants that were present in all editions of civilian Russian Pharmacopoeias starting from 1778. In the 14th edition of the modern Russian Pharmacopoeia, medicinal plants are described in 107 monographs. Altogether, 25 new monographs were included in the 14th edition, and one monograph was excluded in comparison to the 11th edition. Some of the included plants are not endemic to Russia and do not have a history of traditional use, or on the other hand, are widely used in Western medicine. For 15 plants, we described the specificity of their application in Russian traditional medicine along with the claimed dosages and indications in officinal medicine. The pharmacology, safety, and clinical data are summarized and assessed for nine plants, underlining their therapeutic potential and significance for global phytopharmacotherapy. CONCLUSIONS: In this review, we highlight the therapeutical potential of new plants included in the modern edition of the Russian Pharmacopoeia. We hope that these plants will play an imperative role in drug development and will have a priority for future detailed research.

Demonstrating the influence of HTA: INAHTA member stories of HTA impact.

A central function of health technology assessment (HTA) agencies is the production of HTA reports to support evidence-informed policy and decision making. HTA agencies are interested in understanding the mechanisms of HTA impact, which can be understood as the influence or impact of HTA report findings on decision making at various levels of the health system. The members of the International Network of Agencies for HTA (INAHTA) meet at their annual Congress where impact story sharing is one important activity. This paper summarizes four stories of HTA impact that were finalists for the David Hailey Award for Best Impact Story.The methods to measure impact include: document review; claims analysis and review of reimbursement status; citation analysis; qualitative evaluation of stakeholders' views; and review of media response. HTA agency staff also observed changes in government activities and priorities based on the HTA. Impact assessment can provide information to improve the HTA process, for example, the value of patient and clinician engagement in the HTA process to better define the assessment question and literature reviews in a more holistic and balanced way.HTA reports produced by publicly funded HTA agencies are valued by health systems around the globe as they support decision making regarding the appropriate use, pricing, reimbursement, and disinvestment of health technologies. HTAs can also have a positive impact on information sharing between different levels of government and across stakeholder groups. These stories show how HTA can have a significant impact, irrespective of the health system and health technology being assessed.

Analysis on the current quality standards of Chinese materia Medica used in COVID-19 prevention and treatment.

PURPOSE: Traditional Chinese medicine (TCM) has fully engaged and played an essential role in the prevention and treatment of Coronavirus Disease 2019 (COVID-19). This study compares relevant standards on high-frequent Chinese Materia Medicia (CMM) used in this pandemic aiming at reaching a global consensus and ensuring the use of Chinese medicines safely. METHODS: 141 representative Chinese formulas and Chinese Patent Medicines from the National Protocol and the most of Provincial Protocols for controlling COVID-19 in China have been collected to statistical analyze the composition and characteristics of CMM. Among them, the domestic and international standards of 47 varieties with the frequency usage over 10 times were selected to compare their quality requirements in the mainstream pharmacopoeias and international standards. RESULTS: The quality requirements of used CMM for fighting COVID-19 on the terms of overall quality control, marker compounds, and safety indicators showed different patterns in these mainstream pharmacopoeias and international standards. The uniformed and scientific quality standards of CMM were urgently needed to promote global acceptation and trade. CONCLUSIONS: These findings will provide evidence for building unified quality and safety standards that can adapt to the characteristics of CMM and promote international trade, and also will be stated that it is of the highest priority for ISO/TC 249 to formulate high-quality standards that consolidate international consensus to ensure quality and safety of the urgently needed CMM.

[Great Folk Medicine Book from Poljica (Bratulic's Folk Medicine Book)] / Velika Poljicka ljekarusa (Bratuliceva ljekarusa)

The paper presents a folk recipe collection manuscript written by an unknown author in Poljica area, in the 18th century. It is owned by the philologist, historian of literature and bibliophile, Josip Bratulic. Therefore, the author suggests that this recipe collection should bear the name Great folk medicine book from Poljica (Bratulic's folk medicine book). The manuscript is written in Latin script and Croatian language. It consists of 288 pages written in black ink and contains more than 1,100 recipes making it one of the largest known manuscripts. Although well preserved, a small part of it is unreadable. Most recommended recipes are for treating humans and domestic animals, while several recipes contain household tips. The abundance of its content, expressions, and healing instructions add this recipe collection to other similar manuscripts of this region, which create precious part of the Croatian medical, pharmaceutical, and cultural heritage.

[Present and Future of the Japanese Pharmacopoeia in the Clinical Setting and Pharmacy Education].

The Japanese Pharmacopoeia (JP) has played a major role in ensuring the quality of drugs used in Japan as the ultimate source of information on pharmaceuticals. Physicians and pharmacists can reliably use drugs in the clinical setting because they trust the quality when medical treatment progresses smoothly. When there is a problem or challenge, they can refer to the JP. For pharmacists, both the quality of the drug and information on its efficacy and safety are indispensable. Twelve years have passed since the introduction of a 6-year course in pharmacy education, but the weight placed upon the JP has not increased in the educational curriculum. A specific behavioral objective of describing the significance and structure of the JP is included in the revised model core curriculum for pharmacy education. However, fewer than 60% of pharmacy schools have courses specifically focusing on the JP. Professors of physical chemistry, analytical chemistry, pharmaceutics, and pharmacognosy often teach the relevant sections of the JP in their lectures. The foundations of the Japanese manufacturing industry have been questioned because data falsification and inspection fraud have been disclosed in numerous fields. Therefore, ethical education for those who use the JP is a prerequisite for ensuring the reliability of pharmaceuticals.

[Standardization of Crude Drugs for the Japanese Pharmacopoeia].

The latest edition of the Japanese Pharmacopoeia (JP) is the second supplement to the 17th edition containing 324 herbal medicines, of which 176 are crude drugs and 35 are Kampo extracts. Although 148 prescription Kampo extracts are covered by national health insurance, only 35 are listed in the latest JP. However, the sales volume of these 35 Kampo extracts accounts for more than 70% of the total sales volume of Kampo products, as Kampo formulas with higher sales volumes are preferentially listed in the JP. The JP officially defines the origin and description of the listed crude drugs and Kampo extracts and elaborates on their limited values and testing methods. As crude drugs and Kampo extracts are derived from natural products and have the characteristics of traditional medicines, some degree of variation has been experienced during their long-term use, which is one of the crucial differences from chemical drugs. The Japanese Pharmacopoeia Committee on Crude Drugs promotes standardization of the JP by reflecting the actual Japanese market situation. This review explains the characteristics of natural and traditional medicines in crude drug-related items, the JP drafting process and points to be noted, and the significance of listing in the JP.

Mapping Physicians' Experiences with Medicinal Products from Whole Medical Systems: A Descriptive Analysis of the Vademecum of Anthroposophic Medicines.

BACKGROUND: Therapy in whole medical systems involves a large number of medicinal products. One source of knowledge of clinical properties of such products is the experience of therapy providers. A systematic approach to documentation, assessment, and aggregation of physicians' experiences with anthroposophic medicinal products (AMPs) has been developed: the Vademecum of Anthroposophic Medicines. MATERIAL AND METHODS: The Vademecum contains structured information on AMPs, including therapeutic rationale, indications, and therapy recommendations. The information is based on a 17-item questionnaire of physicians' therapy experiences, which is peer-reviewed by an interdisciplinary editorial board. We conducted a descriptive analysis of the Vademecum, 4th edition. RESULTS: The Vademecum comprised 799 different AMPs, used for 1,773 indications, based on 2,543 questionnaires submitted by 274 physicians from 19 countries. The 799 AMPs comprised 52.6% of all AMPs marketed in Germany in 2015-2016. The 1,773 indications corresponded to 544 different ICD-10 three-digit codes, amounting to 29.3% (n = 544/1,854) of all three-digit codes. A total of 30.6% (n = 542/1,773) of indications were supported by ≥2 questionnaires. CONCLUSIONS: The current Vade-mecum covers more than half of all AMPs, used for more than one fourth of all ICD-10 three-digit codes. The Vademecum approach may be relevant for medicinal products from other whole medical systems.

Identification of herbal categories active in pain disorder subtypes by machine learning help reveal novel molecular mechanisms of algesia.

Chronic pain is highly prevalent and poorly controlled, of which the accurate underlying mechanisms need be further elucidated. Herbal drugs have been widely used for controlling various pain disorders. The systematic integration of pain herbal data resources might be promising to help investigate the molecular mechanisms of pain phenotypes. Here, we integrated large-scale bibliographic literatures and well-established data sources to obtain high-quality pain relevant herbal data (i.e. 426 pain related herbs with their targets). We used machine learning method to identify three distinct herb categories with their specific indications of symptoms, targets and enriched pathways, which were characterized by the efficacy of treatment to the chronic cough related neuropathic pain, the reproduction and autoimmune related pain, and the cancer pain, respectively. We further detected the novel pathophysiological mechanisms of the pain subtypes by network medicine approach to evaluate the interactions between herb targets and the pain disease modules. This work increased the understanding of the underlying molecular mechanisms of pain subtypes that herbal drugs are participating and with the ultimate aim of developing novel personalized drugs for pain disorders.