Chinese herbal medicine for treating menopausal symptoms in London women: developing a good practice protocol via the factor analysis of prescribing patterns in a clinical study

The objective of the study described in this paper was to define Chinese medicine formula patterns for the treatment of menopausal women in London. These formula patterns are intended to become best practice guidelines for a future pragmatic randomised controlled trial with the ultimate goal of evaluating the possibility of integrating Chinese medicine treatment strategies for menopausal symptoms into the UK National Health Service. Data from a clinical study that had demonstrated the effectiveness and safety of Chinese medicine in treating 117 perimenopausal women at the Westminster University Polyclinic in London was analysed for symptom occurrence and herb use. The frequency of occurrence of different presenting symptoms and the frequency of use of individual herbs is described, and the patterns of combined herb use and the correlations between these patterns and the presenting symptoms is analysed by means of factor analysis. Treating these use patterns as Chinese herbal medicine formulas, five distinctive formula patterns emerged in the course of this study. While there is some overlap between these formulas and their associated symptom patterns and those described in Chinese medicine textbooks, some formula patterns appear to be unique to London women. This indicates that best practice guidelines for the Chinese medicine treatment of menopausal symptoms, which have been shown to vary cross-culturally, need to be derived from local clinical practice. We discuss the advantages and limitations of the methods – action based clinical study plus factor analysis – we employed to this end

Rhizoma Atractylodis Macrocephalae—Assessing the influence of herbal processing methods and improved effects on functional dyspepsia

Background: The unique pharmaceutical methods for the processing of botanical drugs according to the theory of traditional Chinese medicine (TCM) affect clinical syndrome differentiation and treatment. The objective of this study was to comprehensively elucidate the principles and mechanisms of an herbal processing method by investigating the alterations in the metabolites of Rhizoma Atractylodis Macrocephalae (AMR) processed by Aurantii Fructus Immaturus (AFI) decoction and to determine how these changes enhance the efficacy of aqueous extracts in treating functional dyspepsia (FD).Methods: A qualitative analysis of AMR before and after processing was conducted using UPLC-Q-TOF-MS/MS, and HPLC was employed for quantitative analysis. A predictive analysis was then conducted using a network analysis strategy to establish a botanical drug–metabolite–target–disease (BMTD) network and a protein–protein interaction (PPI) network, and the predictions were validated using an FD rat model.Results: A total of 127 metabolites were identified in the processed AMR (PAMR), and substantial changes were observed in 8 metabolites of PAMR after processing, as revealed by the quantitative analysis. The enhanced aqueous extracts of processed AMR (PAMR) demonstrate improved efficacy in treating FD, which indicates that this processing method enhances the anti-inflammatory properties and promotes gastric motility by modulating DRD2, SCF, and c-kit. However, this enhancement comes at the cost of attenuating the regulation of motilin (MTL), gastrin (GAS), acetylcholine (Ach), and acetylcholinesterase (AchE).Conclusion: Through this series of investigations, we aimed to unravel the factors influencing the efficacy of this herbal formulation in improving FD in clinical settings

Traditional Chinese Medicines and Prescriptions Brought from China to Japan by a Monk (Jianzhen, Japanese: Ganjin): A Historical Review

(1) Background: Japanese Kampo medicine has its origin in ancient Chinese medicine. In 742, a Tang Dynasty monk named Jianzhen (Ganjin) was invited by Japanese clerics to visit Japan and teach commandments in Buddhism. Because of the dangers of the voyage and also other obstacles, he took 11 years to reach Japan on the sixth voyage and he was blind when he arrived in Japan. He was the first person in China to go to Japan to establish the Buddhism commandments, and he was also the first person in Japan to directly teach traditional Chinese medicine. Until now, there have been few reports in English about the details of the Chinese herbal medicines he brought to Japan, including the types of herbal medicines, pharmacological activities, and formulations. In the review, we systematically and comprehensively summarized Jianzhen’s life from the standpoint of his medical and pharmaceutical knowledge and the types and pharmacological activities of Chinese herbal medicines and prescriptions that were brought to Japan by Jianzhen; (2) Methods: A review was made on the relevant literature written by Chinese, Japanese, and English languages regarding the medical and pharmacological knowledge of Jianzhen, the 36 Chinese herbal medicines brought to Japan by Jianzhen, and the pharmacological and therapeutic effects of these 36 herbal medicines, as well as their formulations; (3) Results: The review of the literature proved that Jianzhen’s prescriptions served as a basis for current herbal medicines (Kampo) in Japan. In the process of the literature search, we found a book entitled Jianshangren (Holy Priest Jianzhen)’s Secret Prescription, which recorded the complete prescription of the 36 traditional Chinese medicines Jianzhen brought to Japan; (4) Conclusions: Jianzhen is one of the ancestors of traditional Chinese medicine/Kampo medicine, and he brought traditional Chinese medicine and medical books to Japan for patients. He made important contributions to the development of traditional Chinese medicine in Japan

Emerging Applications of Metabolomics in Traditional Chinese Medicine Treating Hypertension: Biomarkers, Pathways and More

Hypertension is a prevalent, complex, and polygenic cardiovascular disease, which is associated with increased mortality and morbidity. Across the world, traditional Chinese medicine (TCM) constituted by herbal medicine and non-pharmacological therapies is used to assist blood pressure management. Though widely accepted in daily practice, its mechanism remains largely unknown. Recent years saw a number of studies utilizing metabolomics technologies to elucidate the biological foundation of the antihypertensive effect of TCM. Metabolomics is a relatively “young” omics approach that has gained enormous attention recently in cardiovascular drug discovery and pharmacology studies of natural products. In this review, we described the use of metabolomics in deciphering TCM diagnostic codes for hypertension and in revealing molecular events that drive the antihypertensive effect. By corroborating the diagnostic rules, there's accumulating evidence showing that metabolic profile could be the signature of different syndromes/patterns of hypertension, which offers new perspectives for disease diagnosis and efficacy optimization. Moreover, TCM treatment significantly altered the metabolic perturbations associated with hypertension, which could be a crucial mechanism of the therapeutic effect of TCM. Not only significantly rebalances the dynamics of metabolic flux, TCM but also elicits metabolic network reorganization through restoring the functions of key metabolites, and metabolic pathways. The role of TCM in regulating metabolic perturbations will be informative to researchers seeking new leads for drug discovery. This review further envisioned the promises of employing metabolomics to explore network pharmacology, host-gut microbiota interactions and metabolic reprogramming in TCM, and possible herb-drug interactions in this field in future

Inhibition of Th1 and Th17 Cells by Medicinal Plants and Their Derivatives: A Systematic Review.

Searching for new natural drugs that are capable of targeting Th1 and Th17 may lead to development of more effective treatments for inflammatory and autoimmune diseases. Most of the natural drugs can be derived from plants that are used in traditional medicine and folk medicine. The aim of this systematic review is to identify and introduce plants or plant derivatives that are effective on inflammatory diseases by inhibiting Th1 and Th17 responses. To achieve this purpose, the search terms herb, herbal medicine, herbal drug, medicinal plant, phytochemical, traditional Chinese medicine, Ayurvedic medicine, natural compound, inflammation, inflammatory diseases, Th1, Th17, T helper 1 or T helper 17 were used separately in Title/Keywords/Abstract in Web of Science and PubMed databases. In articles investigating the effect of the medicinal plants and their derivatives in inhibiting Th1 and Th17 cells, the effects of eight extracts of the medicinal plants, 21 plant-based compounds and some of their derivatives, and eight drugs derived from the medicinal plants' compounds in inhibiting Th1 and Th17 cells were reviewed. The results showed that medicinal plants and their derivates are able to suppress Th17 and Th1 T cell functions as well as cytokine secretion and differentiation. The results can be used to produce herbal drugs that suppress Th, especially Th17, responses. Copyright © 2017 John Wiley & Sons, Ltd

A review of the botany, ethnopharmacology, phytochemistry, analysis method and quality control, processing methods, pharmacological effects, pharmacokinetics and toxicity of codonopsis radix

Codonopsis Radix, a traditional Chinese medicine in China, has great medicinal and scientific value. Moreover, it can also be used as a health product in daily diet. This paper reviews the botany, ethnopharmacology, phytochemistry, analysis method and quality control, processing methods, pharmacological effects, pharmacokinetics and toxicity related to Codonopsis Radix. The information of Codonopsis Radix is obtained from scientific databases (such as Baidu Scholar, CNKI, Google Scholar, PubMed, Science Direct, Web of Science, and SciFinder Scholar), Chinese herbal classics, Chinese Pharmacopoeia, PhD and MSc dissertations, and so on. The chemical components mainly include alkaloids, alkynes and polyacetylenes, flavonoids, lignans, steroids, terpenoids, organic acids, volatile oils, saccharides and other components, which have a wide range of neuroprotective effects, protection of gastrointestinal mucosa and anti-ulcer, regulation of body immunity, anti-tumor, endocrine regulation, improvement of hematopoietic function, cardiovascular protection, anti-aging and antioxidant effects. In conclusion, this paper summarizes in depth the shortcomings of the current research on Codonopsis Radix and proposes corresponding solutions. At the same time, this paper provides theoretical support for further research on the biological function and potential clinical efficacy of Codonopsis Radix

Evaluating the Individualized Treatment of Traditional Chinese Medicine: A Pilot Study of N-of-1 Trials

Purpose. To compare the efficacy of individualized herbal decoction with controlled decoction for individual patients with stable bronchiectasis. Methods. We conducted N-of-1 RCTs (single-patient, double-blind, randomized, multiple crossover design) in 3 patients with stable bronchiectasis. The primary outcome was patient self-rated symptom scores on visual analogue scales. Secondary outcome was 24-hour sputum volume. A clinical efficacy criterion which combined symptoms score and medication preference was also formulated. Results. All three patients showed various degrees of improvement on their symptoms and one patient’s (Case 3) 24 h sputum volume decreased from 70 mL to 30 mL. However, no significant differences were found between individualized herbal decoction and control decoction on symptoms score, or on 24-hour sputum volume. One patient (Case 2) had clear preference for the individualized herbal decoction over the standard one with the confirmation after unblinding. We therefore considered this case as clinically important. Discussion. N-of-1 trials comply with individualized philosophy of TCM clinical practice and had good compliance. It is necessary to set up clinical efficacy criteria and to consider the interference of acute exacerbation

백년초(Opuntia ficus-indica) 열매 유래 물질의 항궤양 효과, 독성 및 작용 기전

학위논문 (박사) -- 서울대학교 대학원 : 농업생명과학대학 협동과정 농업생물공학전공, 2021. 2. 양태진.위염은 주로 짠 음식과 매운 음식을 주로 먹는 한국 성인들에게 흔한 질병이 다. 일반적으로 증상에는 상복부 통증, 메스꺼움, 구토, 복통, 소화 불량 및 복부 팽 만감이 있다. 위염은 병태생리학적으로 위 공격 인자 (산, 펩신, 헬리코박터 파일로 리)와 위 점막 방어 인자 (위 점액, 중탄산염 분비, 프로스타글란딘 및 점막 세포의 선천적인 저항성) 사이의 불균형으로 발병한다. 위궤양 치료제로 여러 약물이 사용 되고 있다. 그러나 이러한 치료제에는 부작용이 있다. 부작용이 적은 새로운 위염 치료제 개발이 절실히 요구되고 있다. 식물은 잠재적인 치료제를 가지고 있을 것으 로 생각되어 약용 식물에서 새로운 화합물을 찾기 위한 노력이 계속되고 있다. Opuntia ficus-indica (선인장과) (백년초)는 많은 국가에서 전통 의약품으로 사용 되고 있다. 대한민국의 제주도에서는 건강 식품 제조 용도로 널리 재배되고 있다. 본 연구는 백년초 열매 추출물을 위염 치료 천연물의약품으로 개발하기 위해 수행 되었다. OF-80E (백년초 열매 80% 에탄올 추출물)의 항궤양 활성은 에탄올, 비스테로 이드성 항염증제 (인도메타신, 아스피린 및 디클로페낙) 및 스트레스 유발 위염 랫 트 모델을 사용하여 평가하였다. 그 결과는, 시판된 약물인 스티렌정 (Stillen® tablet) 및 뮤코스타정 (Mucosta® tablet)과 비교하였다. 또한, OF-80E의 급성독성, 아만성독성, 유전독성 및 안전성 약리 연구는 인간의 안전한 섭취를 위해 경제협력 개발기구 지 침 및 우수실험실관리 규정에 따라 평가하였다. 마지막으로, 위염 모델에서 OF-80E 의 항궤양작용의 가능한 메커니즘은 생화학 및 분자 분석을 사용하여 설명하였다. AGS 세포를 이용한 아스피린 유도 세포독성 억제 시험을 기반으로 성분 분리 를 통하여 백년초 열매로부터 분리하고, 전자이온화 질량분석법과 핵자기 공명 분 광법을 포함한 분광 분석을 통해 두 종의 활성 화합물을 동정하였다. 두 종의 항궤 양 성분은 플라보노이드인 aromadendrin과 narcissin으로 확인되었다. IC50 값으로 보 면, flavone인 aromadendrin (<0.5 μM)과 flavonol인 narcissin (<0.5 μM)은 다른 flavones인 naringenin (5.9 μM), eriodictyol (>10 μM), taxifolin (1.1 μM) 및 다른 flavonols인 kaempferol, quercetin 및 isokaempfride (>10 μM) 보다 AGS 세포를 이용한 아스피린 유도 세포독 성 억제 효과가 우수하였다. OF-80E는 시판된 약물보다 공격인자에 대해서 위 점막 손상을 보호하는 효과 가 우수하였다. 에탄올, 비스테로이드성 항염증제 및 스트레스 유발 위염 랫트 모델 에서, OF-80E는 시판된 약물에 비해 효과적으로 위 출혈성 병변과 조직학적 조직 손상을 억제하였다. 단회 경구투여 독성연구에서 OF-80E의 개략적인 치사량은 SD 랫트의 암, 수 모두에서 10000 mg/kg 이상으로 확인되었다. 13주 반복 경구투여 독성연구에서 OF- 80E의 무독성량은 SD 랫트의 암, 수 모두에서 2000 mg/kg/day로 확인되었다. 4주 반 복 경구투여 독성 연구에서 OF-80E의 최대내성용량은 비글견 암, 수 모두에서 1500 mg/kg/day로 확인되었다. Salmonella typhimurium과 Escherichia coli를 이용한 복귀돌연 변이 시험에서 OF-80E는 돌연변이를 유발하지 않았다. Chinese hamster lung 세포를 이용한 염색체 이상시험에서 OF-80E는 염색체 이상을 유발하지 않았다. 소핵시험에 서 OF-80E는 동물 골수세포에서 소핵을 유발하지 않았다. OF-80E를 5000 mg/kg 이하 로 설치류에 단회 경구 투여했을 때, ICR 마우스의 중추신경계에 영향을 미치지 않 았고, SD 랫트의 호흡기계에 영향을 미치지 않았다. OF-80E는 500 μg/mL 농도까지 human ether-a-go-go related gene 채널에 영향을 미치지 않는 것으로 보아, OF-80E는 심 혈관계에 미치는 영향이 낮을 것으로 확인되었다. OF-80E는 AGS 세포에서 아스피린에 의해 감소되고, 랫트에서 인도메타신에 의해 감소한 glutathione을 증가시켰다. OF-80E는 AGS 세포에서 아스피린에 의해 감 소한 prostaglandin E2의 농도를 증가시켰다. 인도메타신 유도 위염 랫트에서 감소된 부착성 위점액은 OF-80E의 처리에 의해 합성되고 분비되었다. OF-80E는 인도메타신 유도 랫트의 위 점막에서 myeloperoxidase의 활성을 억제하고, 스트레스 유도 위염 랫트의 위 점막에서 tumor necrosis factor-α를 감소시켰다.Gastritis is a common disease among Korean adults who take mainly very salty and spicy foods. Usually, symptoms include epigastric pain, nausea, vomiting, abdominal pain, indigestion, and bloating. Pathophysiology of gastritis is due to a lack of equilibrium between the gastric aggressive factor (acid, pepsin, and Helicobacter pylori) and the mucosal defense factor (gastric mucus, bicarbonate secretion, prostaglandins, and innate resistance of the mucosal cells). There are several types of medicines used to treat a gastric ulcer. However, these treatments have side effects. There is a pressing need to develop a new gastritis treatment with fewer side effects. Plants are regarded to represent a reservoir of potential therapeutics and therefore the efforts to search for novel compounds from medicinal plants have been continued. Opuntia ficus-indica (Cactaceae) has been used in traditional medicine of many countries. It is widely cultivated in Jeju Island, Korea, for use in the manufacture of health foods. The aim of this study was to develop O. ficus-indica fruits extract as an antiulcer botanical drug. The antiulcer activity of OF-80E (80% ethanol extract of O. ficus-indica fruits) was assessed using the ethanol-, non-steroidal anti-inflammatory drugs (indomethacin, aspirin, and diclofenac)-, and stress-induced gastritis rat models. The results were compared with those of commercially available drugs, Stillen® tablet and Mucosta® tablet. In addition, the acute toxicity, sub-chronic toxicity, genotoxicity, and safety pharmacology studies of OF-80E were analyzed under Organization for Economic Cooperation and Development guideline and Good Laboratory Practice regulations for human safe consumption. Finally, the possible mechanism underlying the antiulcer actions of OF-80E in gastritis models were elucidated using biochemical and molecular analyses. Inhibition of aspirin-induced cytotoxicity in AGS cells assay-guided fractionation of the O. ficus-indica fruits led to the identification of two active compounds through spectroscopic analyses, including electron ionization mass spectrometry and nuclear magnetic resonance spectroscopy. The two antiulcer constituents were the flavonoids aromadendrin and narcissin. Based on the IC50 values, the flavone, aromadendrin (10 μM) and taxifolin (1.1 μM), and flavonols, kaempferol, quercetin, and isokaempfride (>10 μM). OF-80E was more effective than commercially available drugs to protect gastric mucosal damage against aggressive factors. In ethanol-, non-steroidal anti-inflammatory drugs-, and stress-induced gastritis rat models, OF-80E inhibited gastric hemorrhagic lesions and histological tissue damage effectively comparing than commercially available drugs. In a single dose oral toxicity study, the approximate lethal dose of OF-80E in both male and female of Sprague Dawley (SD) rats was higher than 10000 mg/kg. In a 13-week repeated oral toxicity study, the no observed adverse effect level of OF-80E was 2000 mg/kg/day for both sexes of SD rats. In a 4-week repeated oral toxicity study, the maximum tolerance dose of OF-80E was 1500 mg/kg/day for both sexes of beagle dogs. In Salmonella typhimurium and Escherichia coli reverse mutation studies, OF-80E did not cause mutation. In a chromosome aberration test, OF-80E did not cause chromosomal aberration in Chinese hamster lung cells. In micronucleus assay, OF-80E did not induce micronuclei in the mammalian bone marrow cells. Single oral administration of OF-80E to rodent at below 5000 mg/kg did not affect the central nervous system of ICR mice and did not induce adverse effects on the respiratory system of SD rats. OF-80E did not effect on the human ether-a-go-go related gene channel up to the concentration of 500 μg/mL, indicating that the effect of OF-80E on cardiovascular system was to be low. OF-80E increased glutathione reduced by aspirin in AGS cells and decreased by indomethacin in rats. OF-80E increased prostaglandin E2 levels reduced by aspirin in AGS cells. Decreased adherent mucus was synthesized and stimulated, by OF-80E pretreatment in indomethacin-induced gastritis rats. OF-80E inhibited myeloperoxidase activity in indomethacin-induced rat gastric mucosal and reduced tumor necrosis factor-α in stress-induced rat gastric mucosal.Abstract i Contents iv List of Abbreviations xi List of Figures xiv List of Tables xvi Ⅰ. Introduction １ Ⅱ. Literature reviews ４ 1. Gastritis (Gastric ulcer) ４ 1.1. Pathophysiology and risk factors ５ 1.1.1. Helicobacter pylori ６ 1.1.2. Nonsteroidal anti-inflammatory drugs ８ 1.2. Morbidity and mortality ９ 1.3. Diagnosis １０ 1.4. Prevention １２ 2. Therapeutic agents of gastritis １２ 2.1. Histamine H2 antagonists １５ 2.2. Proton pump inhibitors １５ 2.3. Antacids １７ 2.4. Prostaglandin derivatives １８ 2.5. Antimuscarinic agents １８ 2.6. Anti-Helicobacter pylori therapy １９ 2.6.1. Combination therapy ２０ 2.6.2. Anti-Helicobacter pylori vaccines ２１ 2.7. CCKB antagonists ２２ 3. Study of new drug from plant extracts to treat gastritis ２３ 3.1. Plant extracts with antigastritis activity ２３ 3.2. Phytochemicals with antigastritis activity ２７ 3.3. Herbal medicines tested in clinical trials ３０ 4. Opuntia ficus-indica (L.) Miller ３４ 4.1. Nutritional contents and bioactive constituents of Opuntia ficus-indica ３５ 4.2. Biological activities of Opuntia ficus-indica ３９ 4.2.1. Flower ４０ 4.2.2. Fruit/pulp ４１ 4.2.3. Seed ４２ 4.2.4. Peel/skin ４３ 4.2.5. Cladode ４４ Ⅲ. Materials and Methods ４５ 1. Preparation of test materials ４５ 1.1. Instrumental analysis ４５ 1.2. Chemicals and reagents ４６ 1.3. Preparation of O. ficus-indica fruit ethanol extracts ４６ 1.4. Bioassay-guided fractionation and isolation of O. ficus-indica fruits ４７ 1.5. High-performance liquid chromatography with diode array detector and electrospray ionization mass spectrometry chemical analysis ４９ 1.6. High-performance liquid chromatography analysis of narcissin and aromadendrin ５０ 1.7. High-performance liquid chromatography analysis of betanin ５０ 1.8. Mass production of OF-80E (O. ficus-indica fruits 80% ethanol extract) ５１ 2. Evaluation of gastro-protective activity in an in vitro model ５１ 2.1. Gastric AGS cell cultures ５１ 2.2. Ethanol-induced cytotoxicity in AGS cells ５２ 2.3. Aspirin-induced cytotoxicity in AGS cells ５２ 2.4. Determination of reduced glutathione level in AGS cells ５３ 2.5. Determination prostaglandin E2 level in AGS cells ５３ 2.6. Data analysis ５４ 3. Evaluation of gastro-protective activity in an in vivo model ５４ 3.1. Animals ５４ 3.2. Ethanol-induced gastritis rats ５５ 3.3. Indomethacin-induced gastritis rats ５５ 3.4. Aspirin-induced gastritis rats ５５ 3.5. Stress-induced gastritis rats ５６ 3.6. Diclofenac-induced gastritis rats ５６ 3.7. Determination of gastric lesion index ５７ 3.8. Gastric adherent mucus assay ５７ 3.9. Measurement of mucosal myeloperoxidase and tumor necrosis factor-alpha ５８ 3.10. Measurement of reduced glutathione level of mucosa ５８ 3.11. Measurement of histological index of gastric tissue ５８ 3.12. Data analysis ５９ 4. Toxicity studies of OF-80E ５９ 4.1. Single dose oral toxicity study in Sprague Dawley rats ５９ 4.1.1. Animals ５９ 4.1.2. Experimental design ６０ 4.1.3. Data analysis ６１ 4.2. Thirteen-week repeated-dose oral toxicity study with a four-week recovery in Sprague Dawley rats ６１ 4.2.1. Experimental design ６１ 4.2.2. Urine collection and blood sampling ６１ 4.2.3. Urinalysis ６２ 4.2.4. Hematological test ６２ 4.2.5. Clinical biochemistry test ６３ 4.2.6. Histopathology ６３ 4.2.7. Data analysis ６４ 4.3. Four-week repeated-dose oral toxicity study in beagle dogs ６５ 4.3.1. Animals ６５ 4.3.2. Experimental design ６６ 4.3.3. Urine collection and blood sampling ６６ 4.3.4. Urinalysis ６７ 4.3.5. Hematological test ６７ 4.3.6. Clinical biochemistry test ６７ 4.3.7. Histopathology ６８ 4.4. Bacterial reverse mutation test ６８ 4.4.1. Test strains and materials preparation ６８ 4.4.2. Experimental procedures ６９ 4.5. Chromosome aberration test in CHL cells ７０ 4.5.1. Test system ７０ 4.5.2. Experimental procedure ７１ 4.5.3. Evaluation of chromosomal aberration ７２ 4.6. In vivo micronucleus assay ７３ 4.6.1. Test system ７３ 4.6.2. Observations and examinations ７４ 4.7. Effect of OF-80E on the central nervous system in ICR mice ７５ 4.7.1. Test system ７５ 4.7.2. Observations and examinations ７６ 4.8. Effect of OF-80E on the respiratory rate and tidal volume in Sprague Dawley rats ７９ 4.8.1. Test system ７９ 4.8.2. Observations and examinations ７９ 4.9. Effect of OF-80E on human ether-a-go-go-related gene potassium channel expressed in Chinese hamster ovary cells ８０ 4.9.1. Cells cultures ８０ 4.9.2. Preparation of test substances and test solution ８１ 4.9.3. Measurement and analysis ８１ 4.9.4. Data analysis ８２ Ⅳ. Results ８４ 1. Gastro-protective activity of O. ficus-indica fruits in an in vitro model ８４ 1.1. Activity comparisons of various O. ficus-indica fruit ethanol extracts on aspirin-induced cytotoxicity in AGS cells ８４ 1.2. Chemical constituent of O. ficus-indica fruit ethanol extracts ８５ 1.3. Bioassay-guided fractionation and identification of O. ficus-indica fruits ８５ 1.4. Effect of the isolated flavonoids on aspirin-induced cytotoxicity in AGS cells ９１ 1.5. Effect of OF-80E on ethanol-induced cytotoxicity in AGS cells ９２ 1.7. Effect of OF-80E on aspirin-induced cytotoxicity in AGS cells ９３ 1.8. Reduced glutathione and prostaglandin E2 levels in AGS cells treated with OF-80E ９４ 2. Gastro-protective activity of O. ficus-indica fruits in an in vivo model ９６ 2.1. Gastro-protective activity of OF-80E in an ethanol-induced gastritis rat ９６ 2.2. Gastro-protective activity of OF-80E in an indomethacin-induced gastritis rat １００ 2.3. Gastro-protective activity of OF-80E in an aspirin-induced gastritis rat １０２ 2.4. Gastro-protective activity of OF-80E in a stress-induced gastritis rat １０４ 2.5. Gastro-protective activity of OF-80E in a diclofenac-induced gastritis rat １０６ 2.6. Anti-inflammatory and antioxidative activity of OF-80E １０８ 2.6.1. Effect of OF-80E on membrane-bound myeloperoxidase activity １０８ 2.6.2. Effect of OF-80E on tumor necrosis factor-α level １０９ 2.6.3. Effect of OF-80E on reduced glutathione level １０９ 2.7. Effect of OF-80E on adherent mucus level １１０ 3. Toxicity studies of OF-80E １１１ 3.1. Single dose oral toxicity study in Sprague Dawley rats １１１ 3.2. Thirteen-week repeated-dose oral toxicity study in Sprague Dawley rats １１４ 3.2.1. General clinical signs １１４ 3.2.2. Body weights １１６ 3.2.3. Food consumption １１６ 3.2.4. Water consumption １２０ 3.2.5. Urinalysis １２３ 3.2.6. Hematological test １２９ 3.2.7. Clinical blood biochemistry test １３０ 3.2.8. Organ weights １３０ 3.2.9. Necropsy finding １３１ 3.2.10. Histopathological examination １３２ 3.3. Four-week repeated-dose oral toxicity study in beagle dogs １３３ 3.4. Bacterial reverse mutation study １３６ 3.5. Chromosome aberration test in CHL cells １３８ 3.5.1. Results in the presence of S9 mixture １３８ 3.5.2. Results in the absence of S9 mixture １３８ 3.6. Frequency of micronucleated polychromatic erythrocyte and cytotoxicity in an in vivo micronucleus assay １４１ 3.7. Effect of OF-80E on the central nervous system in ICR mice １４３ 3.8. Effect of OF-80E on the respiratory rate and tidal volume in Sprague Dawley rats １４６ 3.9. Effect of OF-80E on human ether-a-go-go-related gene potassium channel expressed in Chinese hamster ovary cells １４８ Ⅴ. Discussion １５０ References １５８ Abstract in Korean １８９Docto

Evolution of the adaptogenic concept from traditional use to medical systems: Pharmacology of stress- and aging-related diseases

Adaptogens comprise a category of herbal medicinal and nutritional products promoting adaptability, resilience, and survival of living organisms in stress. The aim of this review was to summarize the growing knowledge about common adaptogenic plants used in various traditional medical systems (TMS) and conventional medicine and to provide a modern rationale for their use in the treatment of stress-induced and aging-related disorders. Adaptogens have pharmacologically pleiotropic effects on the neuroendocrine-immune system, which explain their traditional use for the treatment of a wide range of conditions. They exhibit a biphasic dose-effect response: at low doses they function as mild stress-mimetics, which activate the adaptive stress-response signaling pathways to cope with severe stress. That is in line with their traditional use for preventing premature aging and to maintain good health and vitality. However, the potential of adaptogens remains poorly explored. Treatment of stress and aging-related diseases require novel approaches. Some combinations of adaptogenic plants provide unique effects due to their synergistic interactions in organisms not obtainable by any ingredient independently. Further progress in this field needs to focus on discovering new combinations of adaptogens based on traditional medical concepts. Robust and rigorous approaches including network pharmacology and systems pharmacology could help in analyzing potential synergistic effects and, more broadly, future uses of adaptogens. In conclusion, the evolution of the adaptogenic concept has led back to basics of TMS and a new level of understanding of holistic approach. It provides a rationale for their use in stress-induced and aging-related diseases