Comprehensive microbiomes and fecal metabolomics combined with network pharmacology reveal the effects of Jichuanjian on aged functional constipation.

BACKGROUND: Functional constipation is a common gastrointestinal disorder especially severely affecting the life quality of the aged. Jichuanjian (JCJ) has been widely used for aged functional constipation (AFC) in clinic. Yet, the mechanisms of JCJ merely scratch the surface with being studied at a single level, rather than from a systematic perspective of the whole. AIM: The purpose of this study was to explore the underlying mechanisms of JCJ in treating AFC from the perspectives of fecal metabolites and related pathways, gut microbiota, key gene targets and functional pathways, as well as "behaviors-microbiota-metabolites" relationships. METHODS: 16S rRNA analysis and fecal metabolomics combined with network pharmacology were applied to investigate the abnormal performances of AFC rats, as well as the regulatory effects of JCJ. RESULTS: JCJ significantly regulated the abnormalities of rats' behaviors, the microbial richness, and the metabolite profiles that were interrupted by AFC. 19 metabolites were found to be significantly associated with AFC involving in 15 metabolic pathways. Delightfully, JCJ significantly regulated 9 metabolites and 6 metabolic pathways. AFC significantly interrupted the levels of 4 differential bacteria while JCJ significantly regulated the level of SMB53. HSP90AA1 and TP53 were the key genes, and pathways in cancer was the most relevant signaling pathways involving in the mechanisms of JCJ. CONCLUSION: The current findings not only reveal that the occurrence of AFC is closely related to gut microbiota mediating amino acid and energy metabolism, but also demonstrate the effects and the underlying mechanisms of JCJ on AFC.

Clinical Effect of Modified Jichuanjian on Senile Patients with Slow Transit Constipation of Spleen-kidney Yang Deficiency Syndrome and Effect on Brain-gut Peptide / 中国实验方剂学杂志

ObjectiveTo observe the clinical effect of modified Jichuanjian on senile patients with slow transit constipation of spleen-kidney yang deficiency syndrome and the influence on brain-gut peptide. MethodA total of 150 senile patients with slow transit constipation were randomized into control group （75 cases） and observation group （75 cases） with the random number table method. The observation group was given modified Jichuanjian （oral， 1 dose/day， 4 weeks）， and the control group was treated with Biantong Capsules （oral， 3 capsules/time， twice/day， 4 weeks）. Data before and after treatment were recorded， including the score of major constipation symptoms， score of Patient Assessment of Constipation Quality of Life （PAC-QOL）， TCM syndrome score， spontaneous complete bowel movements （SCBM）， colonic transit test， serum 5-hydroxytryptamine （5-HT）， 5-HT 4 receptor （5-HT4R）， somatostatin （SS）， and vasoactive intestinal peptide （VIP）， and recurrence. ResultThe total effective rate of the observation group was 93.06% （67/72）， as compared with the 74.65% （53/71） in the control group （χ2=8.974 6， P<0.01）. After treatment， the scores of major constipation symptoms， scores of four dimensions of PAC-QOL， total score of PAC-QOL， and TCM syndrome score were lower than those before treatment in the two groups （P<0.01）， and lower in the observation group than in the control group （P<0.01）. The SCBM in the observation group were more than those in the control group at the 2nd， 3rd， 4th weeks after treatment （P<0.01）. The proportions of residual markers at 24， 48， 72 h after treatment were smaller than those before treatment in the two groups （P<0.01）， and smaller in the observation group than in the control group （P<0.01）. After treatment， the levels of serum 5-HT and 5-HT4R were higher （P<0.01） and the levels of serum SS and VIP were lower （P<0.01） than those before treatment in the two groups. In addition， the levels of serum 5-HT and 5-HT4R in the observation group were higher （P<0.01） and the levels of serum SS and VIP were lower （P<0.01） in the observation group than in the control group. The recurrence in the observation group was 29.85% （20/67） in comparison with the 58.49% （31/53） in the control group （χ2=9.932 4， P<0.01）. ConclusionModified Jichuanjian is effective for senile patients with slow transit constipation of spleen-kidney yang deficiency syndrome， which can alleviate clinical symptoms， improve quality of life， regulate the level of serum brain-gut peptide， improve the colonic transit function， increase SCBM， and reduce the recurrence.

Clarification on Kidney-deficiency Constipation Treated by Classic Prescription Jichuanjian / 中国实验方剂学杂志

Jichuanjian， from the Jing Yue’s Collected Works by Zhang Jingyue， a famous doctor of Ming Dynasty， is composed of Angelica， Achyranthes bidentata， Cistanche deserticola， Alismatis Rhizoma， Shengma and Fructus Aurantii. It is one of the first 100 classic prescriptions published by the National Administration of Traditional Chinese Medicine. The original book states that where the disease is related to deficiency， with impacted stool， medicines such as Xiaohuang prescription cannot be used. If the treatment is needed， Jichuanjian should be applied. Through the textual research of ancient and modern literature， it is found that the efficacy of Jichuanjian has changed from ancient to modern times. In the medical books of the Ming and Qing Dynasties and the modern ones， the treatment is mostly carried out based on the constipation due to deficiency recorded in the original book， while in contemporary times， the treatment of Jichuanjian focuses on kidney （yang）-deficiency constipation and yin-deficiency constipation. Especially since modern times， Jichuanjian is frequently used to treat kidney-deficiency constipation according to the description in the planning textbooks of traditional Chinese medicine colleges and universities， which causes doubts among the authors. To actively respond to the call of General Secretary Xi Jinping that we should strengthen the sorting and excavation of the essence of classical medical books， this paper analyzed and demonstrated the original text and the drug composition， traceability and application by future generations of Jichuanjian based on the Jing Yue’s Collected Works. It was concluded that Jichuanjian was prepared for the treatment of constipation due to weak constitution， fluid deficiency， and emergent purgation， aiming for constipation due to weak constitution and fluid consumption rather than kidney-deficiency constipation described in modern textbooks. As Jichuanjian was developed for similar syndromes， it was reasonable that it was understood by later generations of doctors from the perspective of liver and kidney as well as earth dampness and wood stagnation， which however remains to be further explored and verified in clinic. By combing and discussing the efficacy of Jichuanjian， this paper could provide theoretical basis for the clinical application and modern development of Jichuanjian.

Jichuanjian： A Literature Review / 中国实验方剂学杂志

Jichuanjian，a famous classical formula with definite clinical efficacy in Jingyue Quanshu （《景岳全书》） by ZHANG Jing-yue in the Ming Dynasty， was included in the Catalogue of Ancient Famous Classical Formulas （The First Batch） published by the National Administration of Traditional Chinese Medicine（TCM） in 2018．By means of bibliometrics，43 relevant ancient book data were collected，including 26 ancient books of TCM. The historical origin and development，main indications and symptoms，composition and prescription，dosage，processing，and decoction and administration methods of Jichuanjian were systematically summarized to provide literature support for the development and clinical application of famous classic formulas. It was found that the main symptoms of Jichuanjian were expanded in the past dynasties from deficiency constipation， postpartum constipation， and qi stagnation recorded in the original formula to additional dryness accumulation， blood stasis， Yin constipation， infantile constipation， and lung（intestine）diseases induced by eye diseases. The applicable population of Jichuanjian was extended to children in addition to puerpera and adults，and the disease scope was extended to pediatrics， ophthalmology， and otorhinolaryngology in addition to internal medicine，gynecology and obstetrics．Although Jichuanjian was modified by doctors in the past dynasties，the compatibility of Angelicae Sinensis Radix，Achyranthis Bidentatae Radix，Cistanches Herba，Alismatis Rhizoma，Cimicifugae Rhizoma and Aurantii Fructus has been constant. The decoction and administration methods basically remained unchanged， i.e.， water decoction and administration before meals. Meanwhile， doctors in the Qing Dynasty made a lot of general comments on this formula with little controversy．