Chinese Pharmacopoeia Revisited: A Review of Anti-Depression Herbal Sources

Depression, which can be accompanied by many fatal diseases and a low life quality, has become the leading cause of ill health and disability worldwide. However, Chinese Pharmacopoeia, the most authoritative and evidence-based encyclopedia of Traditional Chinese Medicine (TCM), could contain leads and insights into the development of new antidepressant drugs. In this work, nine herbal medicines with ‘dispel melancholy functions’ specifically documented in Chinese Pharmacopoeia have been comprehensively reviewed with respect to clinical trials, and phytochemical and pharmacological aspects. The nine drugs are Rosae Chinensis Flos, Croci Stigma, Albiziae Cortex and Flos, Roase Rugosae Flos, Curcumae Radix, Hyperici Perforati Herba, Cyperi Rhizoma and Bupleuri Radix. The mechanisms of action of their functional antidepressant compounds, including gallic acid, hypericin, kaempferol, crocetin, crocin, quercetin, luteolin, isorhamnetin, curcumin, hyperforin, adhyperforin, catechin, rutin, puerarin, and saikosaponins A and D, have been collected and discussed. These traditional Chinese herbs and their active compounds provide a promising resource to develop effective new antidepressant drugs in future. Moreover, mechanistic investigations, safety verification and large-scale clinical trials are still expected to finally transform such TCM-based antidepressant resources to new drugs for patients suffering from depression.

Dose-Effect/Toxicity of Bupleuri Radix on Chronic Unpredictable Mild Stress and Normal Rats Based on Liver Metabolomics

Depression, one of the most prevalent psychiatric diseases, affects the quality of life of millions of people. Studies have shown that the lower polar fraction of Bupleuri Radix (PBR) elicited therapeutic effects in chronic unpredictable mild stress (CUMS) rats. In contrast, comparatively mild liver injury was observed in normal rats administered a high PBR dose. It is essential to clarify the effective and safe dose of PBR and its dose-effect/toxicity relationship. In this study, we used the CUMS model to evaluate the effects and toxicities of PBR and to decipher the dose-effect/toxicity relationship and mechanism using the liver metabonomics combined with multivariate statistical analysis. In CUMS rats, PBR improved the depression-like behaviors including reduced body growth rate, anhedonia, and locomotor activities, and markedly reduced the contents of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). In control rats, PBR treatment altered ALT and AST from typical levels. Moreover, the effective dose range for CUMS rats was 12.6–163 g (herb)/kg, the median toxicity dose for CUMS and normal rats were 388 and 207 g (herb)/kg. The toxicological results showed that the cytokeratin-18 fragment level was increased significantly in CUMS rats given with 100 g (herb)/kg PBR. After a comprehensive analysis, the use of PBR dose was determined to be 12.6–50 g (herb)/kg. In CUMS rats, PBR could reverse amino acid metabolism, energy metabolism, sphingolipid metabolism, and β-oxidation of fatty acids to produce an anti-depressant effect in a dose-dependent manner. In control rats, two additional metabolic pathways were significantly perturbed by PBR, including glycerophospholipid metabolism and bile acid metabolism. Moreover, the comprehensive metabolic index including dose-effect index (DEI) and dose toxicity index (DTI) had a remarkable ability (ROC = 0.912, ROC = 0.878) to predict effect and toxicity. The DEI and DTI were used to determine the dose range of effect and toxicity which was shown high concordance with previous results. Furthermore, the CUMS rats possessed a higher toxicity tolerance dose of PBR which was consistent with the theory of “You Gu Wu Yun” in traditional Chinese medicine. The metabonomics techniques combined with correlation analysis could be used to discover indicators for comprehensive evaluations of efficacy and toxicity.

Which East Asian herbal medicines can decrease viral infections?

Whilst Western research for the COVID-19 crisis focuses on vaccination, in East Asia traditional herbal prescriptions are studied for SARS-CoV2 therapy. In Japan, Maoto (Ephedrae herba 4 g, Armeniacae semen 4 g, Cinnamomi cortex 3 g, and Glycyrrhizae radix 2 g, JPXVII) is used based on clinical evidence for its effect on early phase influenza (also caused by RNA viruses) comparable to that of oseltamivir. The Health Ministry of Thailand has approved Andrographis paniculata (Jap. Senshinren) extracts for treatment of COVID-19. Its combination (4 g) with Maoto, Maoto-ka-senshinren, seems most promising for the treatment of viral pandemics. In China, the official guideline for COVID-19 treatment contains TCM medications with antiviral, as well as immunmodulatory and anti-inflammatory effects such as: Qing-Fei-Pai-Du-Tang (Jap. Seihai-haidokuto) contains 21 drugs; Shufeng Jiedu Jiaonang (Bupleuri radix 8 g, Forsythiae fructus 8 g, Glycyrrhizae radix 4 g, Isatidis radix 8 g, Patriniae herba 8 g, Phragmitis rhizoma 6 g, Polygoni cuspidati rhizoma 10 g, Verbenae herba 8 g); Fufang Yuxingcao Heiji (Forsythiae fructus 0.6 g, Houttuyniae herba 6 g, Isatidis radix 1.5 g, Lonicerae flos 0.6 g, Scutellariae radix 1.5 g) first gained prominence during the 2002 SARS epidemic. With no Western medicine available, the following overview discusses efficacy and mechanisms in view of viral entry and replication of different East Asian herbal remedies for COVID-19 treatment.

Quantitative Determination of 7 Saikosaponins in Xiaochaihu Granules Using High-Performance Liquid Chromatography with Charged Aerosol Detection

Bupleuri Radix (Chaihu, in Chinese) is the principal drug in Xiaochaihu granules (XGs) that is a famous Chinese medicine preparation in China. Since previous analytical methods have not focused on the multiactive saikosaponins of Chaihu, it is difficult to effectively control the quality of XG on the market. In this manuscript, the simultaneous determination of 7 saikosaponins (saikosaponins C, I, H, A, B2, G, and B1) in XG by HPLC with charged aerosol detection (CAD) and confirmation by LC-Q-Orbitrap HRMS were described. The saikosaponins were purified on an SPE cartridge and determined on a Waters CORTECTS C18 column (4.6 mm × 150 mm, 2.7 μm) by gradient elution using 0.01% acetic acid aqueous solution and acetonitrile. The results showed good linearity with the r2 values higher than 0.998 for all analytes. The average recoveries at three different concentration levels ranged from 80% to 109% and the intraday and interday precision (relative standard deviations, RSD%) were in the range of 1.0%∼1.9% and 1.4%∼2.1%, respectively. The established HPLC-CAD method was subsequently applied to 15 batches of XG to investigate the batch-to-batch consistency and controllability. The proposed method could potentially be used for the quality control of XG and also be helpful in the quality evaluation of Chaihu and its related preparations.

Bupleuri Radix Prevents the Recurrences of Resected Colonic Polyps by Affecting Angiogenin-2-Induced Protein Kinase B/Akt Signaling

Aim. We aimed to explore the effects of Bupleuri Radix (BR) on the recurrence of resected colonic polyp (CP) by measuring angiogenin-2-induced protein kinase B (Ang PKB)/Akt signaling. Method. The main ingredients of BR were extracted by using ethanol and measured by HPLC. One hundred twenty patients with CP >10 mm who underwent resected surgery were randomly allocated to an aspirin (AG) or a BR medicine (BG) group. The allocation ratio was 1 : 1 and the intervention duration was one year. The recurrence rate of resected CP was investigated and the plasma levels of Ang PKB/Akt and inflammatory cytokines were measured using ELISA kits. After one-year surgery, side effects were recorded. The relationship between the serum levels of the main compounds of BR and plasma levels of Ang PKB/Akt was analyzed. Results. The main ingredients of CP are paeoniflorin, baicalin, saikosaponin A, and bupleurum saponin B2. Recurrence of resected CP was found in 17 patients from the AG group and eight patients from the BG group after one-year follow-up p < 0.05 . The levels of angiogenin-2 II and PKB/Akt in the AG group were higher than those in the BG group p < 0.05 . Meanwhile, BR treatment reduced the plasma levels of TNF-α, IL-1β, and IL-6, and increased the level of IL-10 p < 0.05 . Inflammatory cytokines are important factors that affect the recurrence of resected CP. Serum paeoniflorin, baicalin, saikosaponin A, and bupleurum saponin B2 in BR had a strong negative relationship with the plasma levels of Ang PKB/Akt. Conclusion. BR significantly reduces the recurrence risk of resected CP by affecting Ang PKB/Akt signaling.