ABSTRACT
Zuojinwan is a classic Chinese medicine prescription recorded in the Danxi's Experiential Therapy， with Coptidis Rhizoma and Euodiae Fructus in a ratio of 6 ∶ 1. It can treat symptoms such as liver fire hypochondriac pain， stomach duct pain， vomiting， and acid swallowing. There are many pharmacological studies on Zuojinwan in modern times， especially in the digestive tract， but the prescription also has its unique effect on digestive tract cancer， and its anti-tumor studies mainly focus on colorectal cancer and gastric cancer. Colorectal cancer is the third most common type of cancer in the world and the second deadliest malignancy. At present， a number of studies have shown that the basic pharmacological studies of anti-colorectal cancer by Zuojinwan include the proliferation， apoptosis， invasion， energy metabolism， epigenetics， and drug resistance of colorectal cancer. Alkaloids are the main active ingredients of Zuojinwan， such as berberine， evodiamine， coptisine， palmatine， and rutaecarpine. Compared with the effect of Zuojinwan on colorectal cancer， studies on the effect of berberine and evodiamine on tumor angiogenesis， tumor-promoting inflammation， and intestinal flora are carried out， except the studies on the resistance of berberine and the effect of evodiamine on energy metabolism. In addition， coptisine， palmatine， and rutaecarpine can regulate the proliferation， apoptosis， and metastasis of colorectal cancer cells， the proliferation and apoptosis of colorectal cancer cells， tumor-promoting inflammatory response， and the proliferation， migration， and invasion of colorectal cancer cells， respectively. Moreover， other studies have shown that the combination of berberine and evodiamine can have a synergistic effect on the growth， migration， and invasion of colorectal cancer cells and can reduce the cardiac toxicity induced by evodiamine. Therefore， this paper summarizes the studies on the anti-colorectal cancer mechanism of Zuojinwan and its main monomer components in recent years， so as to provide a theoretical basis for future clinical research and development of new high-efficiency and low-toxicity anti-colorectal cancer drugs and lay a solid foundation for clinical practice.
ABSTRACT
ObjectiveTo explore the effect and mechanism of Zuojinwan （ZJW） in the treatment of ulcerative colitis （UC） through network pharmacology and experimental validation. MethodUsing network pharmacology and molecular docking， the active components and potential mechanism of ZJW in treating UC were preliminarily identified. Forty-eight male C57BL/6J mice were randomly divided into a normal group， a model group， a sulfasalazine group （300 mg·kg-1）， and low-， medium-， and high-dose ZJW groups （1.82， 3.64， 7.28 g·kg-1）. The UC model was induced by dextran sulfate sodium （DSS）， and oral administration of drugs began on the third day of modeling， lasting for 7 days. The general condition of mice was observed daily， and the disease activity index （DAI） was evaluated. Hematoxylin-eosin （HE） staining was performed to observe histopathological changes in colon tissue. Enzyme-linked immunosorbent assay （ELISA） was used to measure the levels of tumor necrosis factor （TNF）-α， interleukin （IL）-6， and IL-10 in mouse serum. The molecular mechanism was validated using Western blot. ResultNetwork pharmacology predicted that the phosphoinositide 3-kinase （PI3K）/protein kinase B （Akt） signaling pathway might be a key pathway in the regulation of UC by ZJW. Molecular docking results showed good binding ability between the key components of ZJW and core targets. Animal experiment results showed that compared with the normal group， the model group had shortened colon length （P<0.01）， increased DAI scores， spleen index， colon tissue pathology scores， and levels of TNF-α and IL-6 in serum （P<0.05， P<0.01）， increased PI3K， phosphorylated Akt （p-Akt）， and B-cell lymphoma-2 （Bcl-2）-associated X protein （Bax） expression in colon tissue （P<0.05， P<0.01）， and decreased serum IL-10 levels and colon tissue Bcl-2 protein expression （P<0.01）. Compared with the model group， the ZJW groups showed significant improvement in UC symptoms， relieved colon tissue pathological damage， downregulated levels of inflammatory cytokines TNF-α and IL-6 in serum （P<0.01）， inhibited expression of PI3K， p-Akt， and Bax proteins in colon tissue （P<0.05， P<0.01）， and increased serum IL-10 levels and colon tissue Bcl-2 protein expression （P<0.01）， with the high-dose group showing the best effect. ConclusionZJW effectively alleviates DSS-induced UC， and its mechanism may be related to the inhibition of the PI3K/Akt signaling pathway and regulation of apoptosis-related protein expression.
ABSTRACT
Zuojinwan originated from Danxi′s Experiential Therapy （《丹溪心法》） in the Yuan dynasty. It is a representative prescription for the treatment of liver fire invading stomach syndrome， and is also one of the typical prescriptions of the anti-adjuvant method of traditional Chinese medicine （TCM）. In this paper， the method of bibliometrics was used to systematically sort out the ancient books of Zuojinwan， and 729 relevant literature data were obtained. After certain retrieval and screening， 57 ancient books of TCM were finally obtained. The statistics and analysis were carried out from the aspects of prescription source， historical evolution， composition， functions， evolution of prescription meaning， prescription dose， and preparation and usage of Zuojinwan. It was found that Zuojinwan was composed of Coptis chinensis rhizoma and Euodia rutaecarpa fructus in a ratio of 6∶1. It was mainly used for the treatment of liver fire invading stomach syndrome. The symptoms included pain in chest and hypochondrium， vomiting and bitter mouth， noisy acid-swallowing， red tongue coating yellow， and pulse string number. Later medical records recorded that Zuojinwan was mostly consistent with the original prescription. It mainly treated various diseases caused by liver fire， including left by liver fire， including left hypochondriac pain， swallowing acid and vomiting acid， tendon hernia and lump， epigastric pain， bitter mouth pulse string， head pain， diarrhea， gonorrhea， cold and hot， abdominal pain， alcohol wet yellowing， silence of oral dysentery and so on. There was little controversy in the analysis of relevant prescriptions. In the past dynasties， pills was mainly used， which was consistent with the original prescription. In modern times， it is mainly water flooding for pills or steamed cakes for pills， warm boiling water to serve 6 g， taking 2-3 g per time， the history is basically the same. In this paper， through the excavation， collation and systematic analysis of the ancient literature of TCM that recorded Zuojinwan， we hope to provide the literature basis for the development， inheritance and utilization of this famous classical formulas.