Anti-diabetic Effect of Zishenwan and Its Herbal Components： A Review / 中国实验方剂学杂志

Zishenwan， also known as Tongguanwan， is composed of three herbs：Anemarrhenae Rhizoma， Phellodendri Chinensis Cortex， and Cinnamomi Cortex， which thus is thought to be the representative formula to clear heat， purge fire， nourish Yin， and tonify Qi， and it is often used for treating anuresis and renal arthralgia. In recent years， this formula has become a commonly used combination of herbs and is used to treat diabetes （consumptive thirst disease） diagnosed with "lower consumption" syndrome. This article systematically reviewed the development of traditional Chinese medicine （TCM） theory for Zishenwan. Moreover， based on modern pharmacological research， the previous studies on the components of Zishenwan， the improvement of diabetes-related diseases by Zishenwan， and the relationship between the single herd of Zishenwan and the treatment of diabetes were summarized， and the chemical components and the mechanisms for treating diabetes by the three herbs were discussed. It is found that Zishenwan can alleviate diabetes and diabetic nephropathy by performing anti-inflammation， enhancing insulin sensitivity， and inhibiting pyroptosis of renal tubular epithelial cells. Three herbs in Zishenwan and several components of them， including mangiferin， timosaponins， berberine， jatrorrhizine， cinnamaldehyde， and cinnamic acid can ameliorate diabetes and maintain stable glycometabolism by a variety of mechanisms such as improving insulin resistance in insulin target tissues， suppressing inflammation， anti-oxidation， regulating lipid metabolism， enhancing insulin secretion， and regulating gut microbiota. This review provides a theoretical foundation and reference for subsequent studies on the mechanisms of the anti-diabetic effect of Zishenwan.

Cinnamomi Cortex Regulates Incretin Effect in Diabetic Rats / 中国实验方剂学杂志

ObjectiveTo observe the pharmacodynamic effects of Cinnamomi Cortex on the incretin effect in the rat model of diabetes mellites （DM） induced by streptozotocin （STZ） and explore the underlying mechanism from glucagon-like peptide-1 （GLP-1） and dipeptidyl peptidase-4 （DPP-4）. MethodForty SD rats were randomly assigned into blank， model， sitagliptin （0.1 g·kg-1）， and low- and high-dose Cinnamomi Cortex （0.45 and 0.9 g·kg-1， respectively） groups. The DM rat model was established by a high-fat diet combined with intraperitoneal injection of 40 mg·kg-1 STZ in other groups except the blank group. The intervention lasted for 8 weeks. The status， body weight， water intake， food intake， and fasting blood glucose （FBG） of the rats were observed and determined. Hematoxylin-eosin staining was employed to reveal the pathological changes of the pancreas， and immunohistochemistry to detect the expression of glucagon in the pancreas. Biochemical assay was employed to measure the serum levels of lipid metabolism indexes such as total cholesterol （TC）， triglyceride （TG）， low-density lipoprotein （LDL）， and high-density lipoprotein （HDL）. Enzyme-linked immunosorbent assay was employed to determine the levels of glycosylated hemoglobin， insulin， glucagon， GLP-1， and glucose-dependent insulinotropic polypeptide （GIP） in rat serum， and Western blot to determine the protein levels of GLP-1 and DPP-4 in the pancreas. ResultAfter 8 weeks of intervention， the model group showed higher body weight， FBG， TC， TG， LDL， glycosylated hemoglobin， glucagon， insulin， and insulin resistance index and lower HDL， GLP-1， and GIP than the blank group （P<0.05， P<0.01）. The Cinnamomi Cortex groups showed lower body weight， FBG， TC， TG， LDL， glycosylated hemoglobin， glucagon， insulin， and insulin resistance index and higher HDL， GLP-1， and GIP than the model group （P<0.05， P<0.01）. The Cinnamomi Cortex groups showed recovered morphology of islet cells and no nucleus aggregation. Compared with the model group， the Cinnamomi Cortex groups showed declined levels of glucagon in the center of islet cells. Compared with the blank group， the model group showed up-regulated protein level of DPP-4 and down-regulated protein level of GLP-1 （P<0.01）. Compared with the model group， the high-dose Cinnamomi Cortex groups showed down-regulated protein level of DPP-4 and up-regulated protein level of GLP-1 （P<0.05）. ConclusionCinnamomi Cortex may reduce blood glucose and improve incretin effect to lower the blood glucose level by regulating DPP-4 and GLP-1 in DM rats.

Experimental study of cardioprotective effects of Cinnamomi Ramulus and Cinnamomi Cortex formula granules on myocardial ischemia/reperfusion injury in rats based on efficacy of "warming and coordinating heart Yang" / 中国中药杂志

This study aimed to parallelly investigate the cardioprotective activity of Cinnamomi Ramulus formula granules(CRFG) and Cinnamomi Cortex formula granules(CCFG) against acute myocardial ischemia/reperfusion injury(MI/RI) and the underlying mechanism based on the efficacy of "warming and coordinating the heart Yang". Ninety male SD rats were randomly divided into a sham group, a model group, CRFG low and high-dose(0.5 and 1.0 g·kg~(-1)) groups, and CCFG low and high-dose(0.5 and 1.0 g·kg~(-1)) groups, with 15 rats in each group. The sham group and the model group were given equal volumes of normal saline by gavage. Before modeling, the drug was given by gavage once a day for 7 consecutive days. One hour after the last administration, the MI/RI rat model was established by ligating the left anterior descending artery(LAD) for 30 min ischemia followed by 2 h reperfusion except the sham group. The sham group underwent the same procedures without LAD ligation. Heart function, cardiac infarct size, cardiac patho-logy, cardiomyocyte apoptosis, cardiac injury enzymes, and inflammatory cytokines were determined to assess the protective effects of CRFG and CCFG against MI/RI. The gene expression levels of nucleotide-binding oligomerization domain-like receptor family pyrin domain protein 3(NLRP3) inflammasome, apoptosis-associated speck-like protein containing a CARD(ASC), cysteinyl aspartate specific proteinase-1(caspase-1), Gasdermin-D(GSDMD), interleukin-1β(IL-1β), and interleukin-18(IL-18) were determined by real-time quantitative polymerase chain reaction(RT-PCR). The protein expression levels of NLRP3, caspase-1, GSDMD, and N-GSDMD were determined by Western blot. The results showed that both CRFG and CCFG pretreatments significantly improved cardiac function, decreased the cardiac infarct size, inhibited cardiomyocyte apoptosis, and reduced the content of lactic dehydrogenase(LDH), creatine kinase MB isoenzyme(CK-MB), aspartate transaminase(AST), and cardiac troponin Ⅰ(cTnⅠ). In addition, CRFG and CCFG pretreatments significantly decreased the levels of IL-1β, IL-6, and tumor necrosis factor-α(TNF-α) in serum. RT-PCR results showed that CRFG and CCFG pretreatment down-regulated the mRNA expression levels of NLRP3, caspase-1, ASC, and downstream pyroptosis-related effector substances including GSDMD, IL-18, and IL-1β in cardiac tissues. Western blot revealed that CRFG and CCFG pretreatments significantly decreased the protein expression levels of NLRP3, caspase-1, GSDMD, and N-GSDMD in cardiac tissues. In conclusion, CRFG and CCFG pretreatments have obvious cardioprotective effects on MI/RI in rats, and the under-lying mechanism may be related to the inhibition of NLRP3/caspase-1/GSDMD signaling pathway to reduce the cardiac inflammatory response.

Aconiti Lateralis Radix Praeparata-Cinnamomi Cortex Combination Alleviates Slow Transit Constipation due to Yang Deficiency in Rats via Regulating VIP/cAMP/PKA/AQP Pathway in Colon / 中国实验方剂学杂志

ObjectiveTo investigate the effect and mechanism of Aconiti Lateralis Radix Praeparata-Cinnamomi Cortex in regulating the intestinal function in the rat model of slow transit constipation （STC） due to yang deficiency via the vasoactive intestinal peptide （VIP）/cathelicidin antimicrobial peptide （cAMP）/protein kinase A （PKA）/aquaporin （AQP） pathway. MethodSD rats were randomized into 6 groups （n=6）， including a control group， a model group， high-， medium-， and low-dose Aconiti Lateralis Radix Praeparata-Cinnamomi Cortex groups， and a prucalopride group. Other groups except the control group were treated with loperamide hydrochloride combined with ice water by gavage for the modeling of STC due to yang deficiency. The number of fecal pellets， time to the first black stool defecation， fecal water content， intestinal propulsion rate， and score of fecal properties were recorded in each group. At the end of the treatment， the colon was stained with hematoxylin-eosin （HE） to reveal the histopathological changes and Alcian blue/periodic acid-Schiff （AB-PAS） to reveal the secretion of colonic mucus. The enzyme-linked immunosorbent assay （ELISA） was employed to measure the level of VIP in the serum. The mRNA level of AQP in the colon was measured by polymerase chain reaction （Real-time PCR）. Immunohistochemical staining was performed to observe the expression of AQPs in the colon and kidney tissues. Western blot was performed to determine the protein levels of cAMP， PKA， and VIP in the colon tissue. ResultCompared with the control group, the model group had longer time to the first black stool defecation, reduced fecal pellets and water content, reduced Bristol Stool Form Scale score and intestinal propulsion rate, and constipation aggravated（P<0.01）. Moreover, increased the intestinal lesions, reduced the mucus secretion, reduce the serum VIP level, up-regulated the expression levels of AQP1 in the colon and kidney tissues, inhibited the expression of AQP3 and AQP9（P<0.01）., and down-regulated the protein levels of cAMP, PKA, and VIP in the colon tissue. Compared with the model group， the high-dose Aconiti Lateralis Radix Praeparata-Cinnamomi Cortex group had shortened time to the first black stool defecation， increased fecal pellets and water content， increased Bristol Stool Form Scale score and intestinal propulsion rate， and alleviated constipation symptoms. Moreover， high-dose Aconiti Lateralis Radix Praeparata-Cinnamomi Cortex reduced the intestinal lesions， increased the mucus secretion， elevated the serum VIP level（P<0.01）.， down-regulated the expression levels of AQP1 in the colon and kidney tissues， promoted the expression of AQP3 and AQP9（P<0.05，P<0.01）， and up-regulated the protein levels of cAMP， PKA， and VIP in the colon tissue. The medium- and low-dose groups had weaker effect than the high-dose group（P<0.01）. ConclusionHigh-dose Aconiti Lateralis Radix Praeparata-Cinnamomi Cortex can improve the intestinal motility and balance the intestinal water and fluid metabolism by up-regulating the VIP/cAMP/PKA/AQP pathway， thereby mitigating the constipation symptoms in the rat model of slow transit constipation due to yang deficiency.

Study on the molecular mechanism of Cinnamomi Cortex-Rehmanniae Radix in preventing and treating osteoporosis based on multi-directional regulation of inflammatory factors, estrogen and bone homeostasis / 药学学报

In this study, the molecular mechanism of Cinnamomi Cortex-Rehmanniae Radix (CR) in the prevention and treatment of osteoporosis (OP) was investigated by integrating compatibility analysis of compound, bioinformatics and metabolomics. The rat OP models were established, and the Micro-CT indexes and pathological sections were comprehensively evaluated. The results showed that compared with the model group, the indexes such as bone mineral density (BMD) and bone volume/tissue volume (BV/TV) were significantly increased after CR treatment (P < 0.05), and the bone trabeculae were arranged into mesh. The results of UHPLC-Q-TOF/MS mainly involved amino acid metabolism, lipid metabolism and estrogen metabolism pathways. Integrating bioinformatics and metabolomics analysis, it was finally found that: ① cinnamic acid and ethylcinnamate inhibit inflammatory factors such as TNF, IL-1β, and IL-13, thereby preventing and treating OP; ② multiple active ingredients of CR target ESR2, PPARG, and CYP19A1, GABRA1 and other targets, regulate cAMP synthesis, AMPK signaling pathway and lipid metabolism, thereby regulating estrogen levels to prevent and treat OP; ③ oleic acid, arachic acid, etc. act on AR, VDR and other targets, and regulate HIF-1 signaling pathway and AGE-RAGE signaling pathway, thereby regulating osteoblasts and osteoclasts, and affecting calcium and phosphorus absorption to maintain bone homeostasis. This study clarified the molecular mechanism of CR in preventing and treating OP from the perspective of multi-directional regulation of inflammatory factors, estrogen and bone homeostasis, and provided theoretical basis for the clinical application of CR and the development of compound. This experiment complied with the ethical standards of animal experiments and was approved by the Animal Ethics Committee of Shaanxi University of Chinese Medicine (No. SUCMDL20210309002).

Research progress in chemical constituents and pharmacological action of Chinese medicine pair of Coptidis Rhizoma- Cinnamomi Cortex / 国际中医中药杂志

Coptidis Rhizoma- Cinnamomi Cortex is a classic couplet medicine of Traditional Chinese Medicine, which has the function of communicating heart and kidney, and has been widely used in clinic. At present, the chemical composition of Coptidis Rhizoma- Cinnamomi Cortex before and after compatibility, in terms of nature, quality and in vivo processes to carry out research. The drug pair has sedative hypnotic, hypoglycemic, antidepressant, antiarrhythmic and other pharmacological effects, involving regulation of neurotransmitters, regulation of inflammatory cytokines, antioxidant, regulation of intestinal flora and other mechanisms. The existing research is still insufficient, such as the study on the changes of material basis after the compatibility of Coptidis Rhizoma- Cinnamomi Cortex, as well as the pharmacological effects of cardiovascular system, lipid metabolism and perimenopausal syndrome. The best compatibility ratio of Coptidis Rhizoma- Cinnamomi Cortex in sedation, hypnosis, hypoglycemic and antidepressant needs further analysis.

Establishment of Near Infrared Quantitative Analysis Model for Four Components in Cinnamomi Cortex / 中国实验方剂学杂志

Objective::To establish a rapid evaluation method for Cinnamomi Cortex decoction pieces by near infrared spectroscopy. Method::The contents of coumarin, cinnamalol, cinnamic acid and cinnamaldehyde in 86 batches of Cinnamomi Cortex of different origins were determined by HPLC. And the NIR spectra of different batches of Cinnamomi Cortex were also collected. With NIR spectrum as independent variable and coumarin, cinnamalol, cinnamic acid and cinnamaldehyde as dependent variables, a quantitative analysis model of four components in cinnamon was established by partial least squares method. Result::The correlation coefficients (r) of coumarin, cinnamic alcohol, cinnamic acid and cinnamaldehyde near infrared quantitative analysis models were 0.952 8, 0.977 7, 0.961 9, 0.992 2, root mean square error of cross(RMSEC) were 0.012 2, 0.006 1, 0.004 3, 0.82 g·g-1, root mean square errorof cross-validation(RMSECV) were 0.015 8, 0.011 2, 0.002 0, 1.481 1 g·g-1, and root mean square error of prediction(RMSEP) were 0.017 8, 0.010 3, 0.010 3, 0.005 5, 1.63 g·g-1. Conclusion::The established NIR quantitative analysis model of four active ingredients in Cinnamomi Cortex slices has a good accuracy, and provides a basis for rapid evaluation of the quality of Cinnamomi Cortex slices.

Anti-melanogenesis and Anti-inflammatory Effects of Cinnamomi Cortex Extract In Vitro / 대한피부과학회지

BACKGROUND: Many researchers have sought to identify safe, natural herbal extracts that exert an anti-melanogenesis effect. Cinnamomi cortex has been widely used as a herbal medicine in Asia and Europe. OBJECTIVE: To confirm the inhibitory effects of Cinnamomi cortex extract against melanogenesis and inflammation and to elucidate the underlying mechanism of these actions. METHODS: Effects of Cinnamomi cortex extract on melanin synthesis and tyrosinase activity in B16F10 melanoma cells were evaluated using an ELISA reader. Tyrosinase and MITF protein expression was determined using western blotting. Nitric oxide production in RAW 264.7 cells was measured using Griess reaction. PGE₂ was assayed with an ELISA kit. RESULTS: Cinnamomi cortex extracts inhibited melanin synthesis, tyrosinase activity, and MITF and tyrosinase expression through regulation of the ERK and CREB genes in α-MSH-induced B16 melanoma cells. In addition, Cinnamomi cortex extracts inhibited the expression of NO, PGE₂, and pro-inflammatory cytokines in lipopolysaccharide-induced RAW 264.7 cells. CONCLUSION: We suggest that Cinnamomi cortex may be a potentially useful agent for treating inflammatory skin diseases such as hyperpigmentation based on its inhibitory effects against melanin synthesis and inflammation response in vitro.

Traditional Chinese Medicine Cognition and Modern Pharmaceutical Research on Effect of Cassia Twig and Cinnamomum Cassia in Treating Paralysis / 中国实验方剂学杂志

Cinnamomi Ramulus and Cinnamomi Cortex are widely used to treat paralysis in traditional Chinese medicine (TCM). There are numerous and complicated relative records in ancient literatures. Doctors often use Cinnamomi Ramulus to dispel wind and cold, remove blood stasis and combine with warm-natured and heat-natured herbs to treat excess paralysis and early-stage paralysis. And Cinnamorni Cortex is used to warm and invigorate kidney Yang and combine with warm-benefiting herbs to treat deficiency paralysis and chronicle paralysis. However, modern pharmaceutical studies reported that their active substances are almost the same. The active substances in Cinnamomi Cortex are more than those in Cinnamomi Ramulus. The mechanisms of treating paralysis include:suppressing inflammation and regulating immunity by down-regulating nuclear factors(NF)-κB, mitogen activated protein kinase(MAPK), Janus kinase-signal transducers/activators of transcription(JAK/STAT) signaling pathways, regulating cell proliferation by inhibiting the proliferation of fibroblasts, osteoclasts and bone marrow mesenchymal stem cells and promoting the proliferation of osteoblast, resisting oxidation by scavenging oxygen free radicals, regulating pain by mediating TRPA1 and TRPV1,and enhancing substance metabolism and losing weight by regulating the secretion of intestinal hormones (Ghrelin, GLP-1) and improving insulin resistance. The main active ingredient Cinnamaldehyde is unstable in vivo and easily oxidized to cinnamic acid. The toxicity of the two medicines and their components are relatively low. This paper reviews and analyses relative records in ancient literatures, traditional Chinese medicine cognition of their effects in treating paralysis, the achievements and problems of chemical,pharmacological,pharmacokinetic and toxicological researches in recent years, with the aim to provide theoretical basis for further research and application.

Effects of different Chinese meteria medica pair on regulation of adrenal function in mice with hydrocortisone-induced syndrome / 中草药

Objective: To study the effects of different Chinese materia medica combinations on the regulation of adrenal function. Methods Mice with 1.65 mg/(kg•d) hydrocortisone for 14 d to induce drug-induced syndrome was treated synchronously with assissting yang and dissipating cold (Aconm Lateralis Radix Praeparaia-Cinnamomi Cortex), nourishing yin and reducing fire (Anemarrhenae Rhizoma-Phellodendri Chinensis Cortex), tonifying qi and promoting fluid production (Ginseng Radix et Rhizoma-Astragali Radix), and tonifying blood and benefiting spirit (Rehmanniae Radix Praeparata-Corni Fructus). The body mass of mice was dynamically observed every day, and the characteristic information such as body mass, holding power, axillary temperature, activity degrees of open field, and infrared temperature were detected by the experimental methodology of mice syndrome differentiation; The mice were sacrificed whose spleen, thymus was weighed and the organ index was calculated. Serum corticosterone, ACTH, adrenaline, and noradrenaline were measured by ELISA. The gene expressions of Star, Cyp11a1, Cyp21a1, Cyp11b1, Cyp11b2, Dbh, Ddc, Pnmt, and Th in the adrenal were detected by real-time fluorescent quantitative PCR. The protein’s expressions of LDLR, SRB1, and StAR were detected by Western blotting. Results:The effects of four different treatments on the reduction of body weight and body temperature caused by hydrocortisone were not significant. The holding power of mice in Aconm Lateralis Radix Praeparaia-Cinnamomi Cortex group was significantly higher than that of hydrocortisone group (P < 0.05). Compared with the hydrocortisone group, the serum corticosterone content of mice in Anemarrhenae Rhizoma-Phellodendri Chinensis Cortex group increased significantly (P < 0.01); The genes expression of Star, Cyp11b1, and Cyp11b2 was significantly up-regulated (P < 0.05, 0.01); The proteins expression of SRBI and StAR were significantly up-regulated. Conclusion: The nourishing yin and purging fire treatment group (Anemarrhenae Rhizoma-Phellodendri Chinensis Cortex) is the best to correct and protect the adrenal cortex function in mice with hydrocortisone induced syndrome at low dose.

Research on quality standard of processed Cinnamomi Cortex decoction pieces containing volatile oil / 中国中药杂志

To build the quality standard of processed Cinnamomi Cortex standard decoction and provide quality reference for Cinnamomi Cortex formula granules. Fourteen batches of Cinnamomi Cortex standard decoction pieces were prepared according to the preparation requirements for standard decoction of Chinese herbal medicine containing volatile oil. With cinnamaldehyde as the quantitative index, the transfer rate and extraction rate were calculated; pH value was determined and HPLC fingerprint analysis method was established. By the measurement of 14 batches of standard decoction, the transfer rate ranged from 25.0% to 68.4%; the extraction rate was at a range of 3.7% to 10.1% and pH was 3.72 to 5.48. Then the Similarity Evaluation System for Chromatographic Fingerprint of Traditional Chinese Medicine (2012A) was used to analyze and compare the fingerprints. Four common peaks were determined and three were identified including coumarin (peak 1), cinnamic acid (peak 2) and cinnamaldehyde (peak 3). Moreover, the similarity was 1.0. This study established an HPLC fingerprint analysis method of processed Cinnamomi Cortex standard decoction. The method showed good precision, stability and repeatability in fingerprint analysis, with significance in identification.

Comparative study on different processes for Chinese materia medica Moutan Cortex and Cinnamomi Cortex formula granules containing volatile components / 中草药

Objective: To study the influence on the volatile components of Chinese materia medica (CMM) Moutan Cortex and Cinnamomi Cortex formula granules produced by different preparative processes. Methods: The different preparative processes were compared by determining the content of paeonol in Moutan Cortex formula granule and cinnamaldehyde in Cinnammi Cortex formula granule by HPLC. Results: The contents of paeonol in Moutan Cortex formula granule and cinnamaldehyde in Cinnamomi Cortex formula granule produced by conventional process were significantly lower than those by the other processes, which was carried out as follows: extracting the volatile oil firstly, then drying the herb residue extract, adding the volatile oil by spaying directly or cyclodextrin inclusion finally. Conclusion: The best process of CMM Moutan Cortex and Cinnamomi Cortex formula granules containing volatile components was as follows: extracting the volatile components firstly, then decocting the residues, and the volatile components was enclosed before adding in the granulation.

Authentication of raw material for edible and medicinal cinnamon based on plastid Intergenic Region ps-bA-trnH / 中国药学杂志

OBJECTIVE: To introduce DNA barcoding based on plastid intergenic region psbA-trnH to authenticate medicinal and edible materials Cinnamon cassia to promote the standard practice of medication and foods. METHODS: The genomic DNA of eight Cinnamomum species were extracted successfully. The Kimura 2-parameter (K2P) distances were calculated and phylogenetic tree was constructed using software MEGA 5.0. RESULTS: The sequence length of the psbA-trnH of Cinnamomum cassia was 368 bp. The ps-bA-trnH intra-specific genetic distance of C. cassia was highly conservative, which was shorter than the interspecific ones. The NJ tree indicated that Cinnamomi Cortex could be distinguished from its adulterants obviously. CONCLUSION: The psbA-trnH intergenic spacer can be used to distinguish Cinnamomi Cortex from its adulterants accurately.