A review of patent literature on the regulation of glucose metabolism by six phytocompounds in the management of diabetes mellitus and its complications / 中西医结合学报

Diabetes mellitus is a chronic disease, typified by hyperglycemia resulting from failures in complex multifactorial metabolic functions, that requires life-long medication. Prolonged uncontrolled hyperglycemia leads to micro- and macro-vascular complications. Although antidiabetic drugs are prescribed as the first-line treatment, many of them lose efficacy over time or have severe side effects. There is a lack of in-depth study on the patents filed concerning the use of natural compounds to manage diabetes. Thus, this patent analysis provides a comprehensive report on the antidiabetic therapeutic activity of 6 phytocompounds when taken alone or in combinations. Four patent databases were searched, and 17,649 patents filed between 2001 and 2021 were retrieved. Of these, 139 patents for antidiabetic therapeutic aids that included berberine, curcumin, gingerol, gymnemic acid, gymnemagenin and mangiferin were analyzed. The results showed that these compounds alone or in combinations, targeting acetyl-coenzyme A carboxylase 2, serine/threonine protein kinase, α-amylase, α-glucosidase, lipooxygenase, phosphorylase, peroxisome proliferator-activated receptor-γ (PPARγ), protein tyrosine phosphatase 1B, PPARγ co-activator-1α, phosphoinositide 3-kinase and protein phosphatase 1 regulatory subunit 3C, could regulate glucose metabolism which are validated by pharmacological rationale. Synergism, or combination therapy, including different phytocompounds and plant extracts, has been studied extensively and found effective, whereas the efficacy of commercial drugs in combination with phytocompounds has not been studied in detail. Curcumin, gymnemic acid and mangiferin were found to be effective against diabetes-related complications. Please cite this article as: DasNandy A, Virge R, Hegde HV, Chattopadhyay D. A review of patent literature on the regulation of glucose metabolism by six phytocompounds in the management of diabetes mellitus and its complications. J Integr Med. 2023; 21(3): 226-235.

Herbal Textual Research on Zingiberis Rhizoma Recens in Famous Classical Formulas and Its Quality Evaluation / 中国实验方剂学杂志

ObjectiveTo provide references for the selection of Zingiberis Rhizoma Recens on the research of famous classical formulas and the reasonable uses for medicines and foods through herbal textural research and quality analysis of Zingiberis Rhizoma Recens from main producing areas in China. MethodBy consulting the ancient and modern literature， the name， origin， producing areas， harvest time， processing methods of Zingiberis Rhizoma Recens were summarized. According to the 2020 edition of Chinese Pharmacopoeia， the contents of 6-gingerol， 8-gingerol， 10-gingerol， and volatile oil in Zingiberis Rhizoma Recens samples were determined. ResultHerbal textural research indicated that medicinal Zingiberis Rhizoma Recens originated from the fresh rhizome of Zingiber officinale. Before Tang dynasty， Zingiberis Rhizoma Recens produced in Sichuan was the best. In the Song dynasty， Zingiberis Rhizoma Recens produced in Sichuan， Zhejiang， and Anhui was of excellent quality. The cultivation of Zingiberis Rhizoma Recens in Shandong developed during the Ming and Qing dynasties. From ancient times to the present， the harvest period extended from the autumnal equinox to the winter solstice. Quality evaluation standards of Zingiberis Rhizoma Recens were essentially the same in ancient and present documents， as those with little gluten or gluten-free and strong pungency were preferred. After determination， the contents of 6-gingerol， 8-gingerol， and 10-gingerol in 44 samples were qualified in 27 samples， with a qualified rate of 61.4%. Among them， 17 samples were unqualified in the total contents of 8-gingerol and 10-gingerol. Among these qualified samples， the content of 6-gingerol ranged from 0.067% to 0.255%， and the total contents of 8-gingerol and 10-gingerol ranged from 0.040% to 0.131%. The content of volatile oil in 36 samples were qualified in 33 samples， with a qualified rate of 91.7%. Among the qualified samples， the content of volatile oil ranged from 0.175% to 0.410%. ConclusionZingiberis Rhizoma Recens has been used as medicines and foods since ancient times， and the genuine producing areas are consistent in ancient and present times， while the quality of the products， especially the medicinal Zingiberis Rhizoma Recens， should be monitored. Medicinal Zingiberis Rhizoma Recens planted in Leshan city of Sichuan province contains high contents of effective components， followed by Qujing and Wenshan cities of Yunnan province. Zingiberis Rhizoma Recens planted in Shandong and other places is mostly edible.

In Vitro Pharmacokinetics and Pharmacodynamic Evaluation of Jiaojiang Cataplasms / 中国实验方剂学杂志

ObjectiveTo study the in vitro kinetics of Jiaojiang cataplasms and evaluate its pharmacodynamics， so as to provide a feasible basis for the development of this preparation. MethodThe improved Franz diffusion cell was used for the in vitro release in semipermeable membrane and transdermal absorption in in vitro mouse skins. The contents of hydroxy-α-sanshool， 6-gingerol， ginsenoside Rb1 were determined by high performance liquid chromatography （HPLC）， to evaluate the in vitro release and transdermal absorption of Jiaojiang cataplasms. The mobile phase of 6-gingerol and hydroxy-α-sanshool was water-acetonitrile-methanol （2∶1∶1） with the detection wavelength of 280 nm. The mobile phase of ginsenoside Rb1 was acetonitrile-0.1% phosphoric acid aqueous solution （31∶69） with the detection wavelength of 203 nm. A mouse intestinal paralysis model was established， and mice were randomly divided into five groups， namely sham operation group， model group， domperidone group （3.9 mg·kg-1） and high- and low-dose groups of Jiaojiang cataplasms （6.2， 3.1 g·kg-1， measured by crude drug dosage）， to observe the effect of this preparation on gastrointestinal propulsion function. ResultAverage release rates of hydroxy-α-sanshool， 6-gingerol and ginsenoside Rb1 at 24 h were 16.41， 4.23， 4.15 μg∙cm-2∙h-1， the average transdermal rates of them at 24 h were 2.31， 0.64， 0.29 μg∙cm-2∙h-1， their skin retention values were 19.56， 3.59， 1.61 μg， respectively. According to the Ritger-Peppas equation， the release of hydroxy-α-sanshool， 6-gingerol， ginsenoside Rb1 was non-Fick diffusion. The high-dose group of Jiaojiang cataplasms could improve intestinal function of model mice after small intestinal friction injury， and promote intestinal peristalsis and small intestinal propulsion rate （P<0.05）. ConclusionJiaojiang cataplasms has in vitro release and transdermal properties， the in vitro release conforms to Higuchi equation， and transdermal absorption behavior conforms to zero-order kinetic equation， which can improve the postoperative function of the small intestine and the propulsion function of small intestine. It preliminarily indicates that the preparation has certain clinical development value.

Quality markers of Zingiberis Rhizoma Carbonisata before and after processing / 中国中药杂志

Based on the previous research results of our group and literature research, the chemical components, mechanisms, pharmacodynamics, and pharmacokinetics of Zingiberis Rhizoma Carbonisata were summarized to determine the quality markers(Q-markers) of Zingiberis Rhizoma Carbonisata and Zingiberis Rhizoma. Our research group has clarified the differential components of Zingiberis Rhizoma Carbonisata and Zingiberis Rhizoma, the meridian-warming hemostatic effect of Zingiberis Rhizoma Carbonisata, the related targets and pathways of the effect, the endogenous biomarkers of Zingiberis Rhizoma Carbonisata, and the hemodynamic processes of Zingiberis Rhizoma Carbonisata and Zingiberis Rhizoma. Moreover, based on high-performance liquid chromatography-diode array detector-electrospray ionization mass spectrometry(HPLC-DAD-ESIMS), a method for determining the content of Q-mar-kers was established. In conclusion, the study finally determined that gingerone, 6-shogaol, and diacetyl-6-gingerol were the Q-mar-kers of Zingiberis Rhizoma Carbonisata decoction pieces, and 6-gingerol, 8-gingerol, and 10-gingerol were Q-markers of Zingiberis Rhizoma decoction pieces. The result is expected to provide a reference for the establishment of quality standards for Zingiberis Rhizoma Carbonisata decoction pieces and Zingiberis Rhizoma decoction pieces.

6-Gingerol ameliorates adipose tissue insulin resistance in aging rats / 中国中药杂志

This study investigated the effects and mechanisms of 6-gingerol on adipose tissue insulin resistance in naturally aging rats with glycolipid metabolism disorders. Twenty-seven aging male SD rats were randomly divided into a model group(aged, n=9) and two groups treated with 6-gingerol at 0.05 mg·kg~(-1)(G-L, n=9) and 0.2 mg·kg~(-1)(G-H, n=9). Six young rats were randomly assigned to a normal control group(NC). Rats were treated for seven weeks by gavage. Non-esterified fatty acid(NEFA) and insulin content was determined by enzyme-linked immunosorbent assay(ELISA), and adipose tissue insulin resistance index(Adipo-IR) was calculated. HE staining was used to observe the size of adipocytes in epididymal white adipose tissue(eWAT). The gene and protein expression levels of adiponectin receptor 1(AdipoR1), AMP-activated protein kinase α(AMPKα), phosphorylated AMPK(p-AMPKα~(Thr172)), peroxisome proliferator-activated receptor-γ coactivator-1α(PGC-1α), phosphatidylinositol 3-kinase(PI3 K), protein kinase B(Akt), phosphorylated Akt(p-Akt~(Ser473)), tumor necrosis factor-α(TNF-α), c-Jun N-terminal kinase 1/2(JNK1/2), phosphorylated JNK1/2(p-JNK~(Thr183/Tyr185)), interleukin-1β(IL-1β), and interleukin-6(IL-6) in adiponectin(APN), insulin, and inflammatory factor signaling pathways were detected by Western blot and real-time RCR, respectively. The results showed that 6-gingerol at a high dose could significantly decrease the fasting plasma content of NEFA and insulin and reduce Adipo-IR. Additionally, 6-gingerol at a high dose significantly increased the protein and mRNA expression of APN, AdipoR1, PGC-1α, and PI3 K in eWAT, elevated the relative expression of p-AMPK~(Thr172) and p-Akt~(Ser 473), reduced the protein and mRNA expression of TNF-α, IL-1, and IL-6 in eWAT, and decreased the relative expression of p-JNK1 and p-JNK2. This study reveals that 6-gingerol can improve insulin sensitivity of adipose tissues in aging rats with glycolipid metabolism disorders, and this effect is presumedly achieved by enhancing the PI3 K/Akt signaling pathway, inhibiting adipose tissue inflammation, increasing APN synthesis, enhancing AdipoR1 expression, and activating its downstream AMPK/PGC-1α signaling pathway.

Progress in protective effect and mechanism of 6-gingerol on myocardial ischemia/reperfusion injury / 中国药理学与毒理学杂志

The morbidity and mortality of cardiovascular diseases are very high, which has attracted more and more attention all over the world. Common treatment methods for clinical treatment of acute myocardial infarction include direct percutaneous coronary intervention and coronary artery bypass grafting, which can quickly restore blocked coronary blood flow and reduce the infarct size. However, the inevitable ischemia/reperfusion injury will occur during the recovery of coronary blood flow, its pathological mechanism is complicated, and the Western medicine countermeasures are very limited. Among the current drugs for the treatment of cardiovascular diseases, traditional Chinese medicine has become a research hotspot due to its multiple targets, safety, and low side effects. Ginger is the fresh rhizome of Zingiber offici?nale Rosc., a perennial herbaceous plant in the ginger family. It is a dual-purpose resource of medicine and food. Ginger has the functions of relieving the appearance and dispelling cold, warming up and relieving vomiting, resolving phlegm and relieving cough, and relieving fish and crab poison. The chemical components of ginger mainly include volatile oil, gingerol, diphenylheptane, etc.. Among them, 6-gingerol, as the main active component of gingerols, has obvious phar?macological effects in myocardial protection, anti-oxidation, anti-inflammatory, etc.. Studies have shown that 6-gingerol protects myocardium mainly through anti-oxidative stress, anti-inflammatory, inhibiting cell apoptosis, and preventing cal?cium influx. ① Anti-oxidative stress: oxidative stress is a state where oxidation and anti-oxidation in the body are out of balance, and it is also an important factor leading to myocardial damage. Many studies have confirmed that 6-gingerol has an antioxidant effect, and it is considered a natural antioxidant. 6-gingerol can significantly reduce the degree of oxi?dative stress and the level of reactive oxygen species caused by cardiomyocyte damage, and has a significant cardiopro?tective effect. ② Anti-inflammatory: inflammation can cause substantial cell damage and organ dysfunction, which is another important cause of myocardial damage. 6-gingerol can reduce the levels of inflammatory factors such as inter?leukin-6, interleukin-1β, and tumor necrosis factor-αin cardiomyocytes, and at the same time inhibit the TLR4/NF-κB sig?naling pathway, an important regulatory pathway of inflammation, showing that it may improve myocardial damage through anti-inflammatory effects. ③ Inhibition of apoptosis: apoptosis is a complex and orderly process in the autono?mous biochemical process of cells, and one of the main mechanisms of myocardial injury. This process can be roughly divided into three pathways: mitochondria, endoplasmic reticulum, and death receptors. Among them, the mitochondrial pathway plays an important role, and Bcl-2 and Bax located upstream of this pathway can regulate the entire process of cell apoptosis by regulating the permeability of the mitochondrial membrane. Studies have found that the preventive application of 6-gingerol can reduce cell damage, reduce the number of apoptotic cells, reduce the activity of Bax and caspase-3, and increase the expression of Bcl-2. Therefore, 6-gingerol pretreatment can reduce the damage of cardio?myocytes, and its mechanism may be related to the inhibition of apoptosis.④Prevent calcium influx:calcium overload is involved in the pathogenesis of myocardial ischemic injury, which may be related to excessive contracture, arrhythmia, and mitochondrial Ca2+accumulation that impairs myocardial function. 6-gingerol inhibits the increase of intracellular Ca2+concentration by inhibiting L-type calcium current, thereby reducing extracellular Ca2+ influx, thereby avoiding calcium overload and playing a cardioprotective effect. In summary, 6-gingerol can effectively treat and improve myocardial isch?emia/reperfusion injury, and it has great development potential in the fields of medicine and health products.

Validation Of Reversed-Phase High-Performance Liquid Chromatography Method For Simultaneous Determination Of 6-, 8-, 10-Gingerols And 6-Shogaol From Ginger Extracts

Objective: Development and validation of a High-Performance Liquid Chromatography (HPLC) method for the simultaneous estimation of 6-, 8-, 10-Gingerols and 6-Shogaol in ginger extract using authentic standards. Methods: The chromatographic separation was achieved by using a C18 column and a mobile phase composed of acetonitrile, ortho-phospohoric acid in water and methanol. The proposed method was validated in terms of the analytical parameters such as specificity, accuracy, precision, linearity, range, the limit of detection (LOD) and limit of quantification (LOQ) according to ICH guidelines. Results: Linear calibration curves were obtained over concentration ranges of 10-250 µg/ml for 6-, 8-, 10-gingerols and 6-shogaol with determination coefficients more than 0.99 for each analyte. Intra and inter-day precisions of the method were found to be below 2% for each analyte, with relative standard deviation (% RSD) values in the range of 0.47 to 1.55% for 6-gingerol, 0.44 to 1.51% for 8-gingerol, 0.24 to 1.90% for 10-gingerol and 0.25 to 1.67% for 6-shogaol. The percentage recovery of gingerols and shogaol was obtained with an average of 99.53%, 99.97%, 100.13% and 100.53% respectively, which was well within acceptance range. Conclusion: Simple, accurate, precise and rapid HPLC method was developed for the simultaneous analysis of 6-, 8-, 10-gingerols and 6-shogaol and validated in accordance with ICH guidelines. The developed method was found to be suitable for the standardization of herbal extracts and polyherbal formulations for the content of 6-, 8-, 10-gingerols and 6-shogaol.

Five new gingerol compounds from Zingiberis Rhizoma / 药学学报

We separated and purified five chemical constituents of dried ginger by Diaion HP-20, Sephadex LH-20, silica gel and semi-preparative high performance liquid chromatography. Five gingerols were identified by physicochemical properties and MS and NMR spectroscopy techniques: 4-(2-butyl-6-methyl-4H-pyran-4-yl)-2-methoxyphenol (1), 4-(2-hexyl-6-methyl-4H-pyran-4-yl)-2-methoxyphenol (2), 1-(4-hydroxy-3-methoxyphenyl)tridecane-3,5-diol (3), [10]-gingerdiol (4) and 1-[1-(4-hydroxy-3-methoxy phenyl)-3-oxodecan-5-yl]pyrrolidin-2-one (5a, 5b). Compounds 1-3, 5a, 5b are new compounds.

Effect and mechanism of 6-gingerol on invasion and migration of HPV-positive and negative cervical cancer cells / 解放军医学杂志

Objective To observe the inhibitory effect of 6-gingerol on the invasion and migration of human papilloma virus (HPV)-positive and HPV-negative cervical cancer cells, and explore the possible mechanism. Methods Human HPV-positive cervical cancer cells (HeLa) and HPV-negative cells (C33A) were cultured, and added with 6-gingerol at different concentration of 0, 5, 10, 20, 50 μmol/L, the untreated cells play as control, then cultured for 24 h. 10 μmol/L 6-gingerol was determined as the best concentration, then all the cells were treated with 10 μmol/L 6-gingerol for 24 h, 48 h and 72 h respectively. The cell proliferation was detected by MTS method, and cell scratch test was performed to detect the effect of 6-gingerol on cell migration ability. The effect of 6-gingerol on cellular invasion was detected by Transwell chamber. Western blotting was used to detect the expression of matrix metalloproteinase MMP-2, MMP-9, E-cadherin and N-cadherin. Results MTS assay showed that the activity of HeLa and C33A cells decreased with the increase of 6-gingerol concentration and action time, while the activity of HeLa cells decreased more significantly than that of C33A cells at different concentrations or time points. Transwell invasion chamber test showed that the HeLa cells treated with 6-gingerol for 24 h and 48 h, and C33A cells treated with 6-gingerol for 48 h, the cellular invasion ability decreased significantly. The scratch test revealed that the wound healing rate decreased significantly of HeLa cells 24 h and 48 h after 6-carbenol action and of C33A cells 48 h after 6-carbenol action. Western blotting results showed that, treating with 10 μmol/L of 6-gingerol for 24 h, the expressions of E-cadherin increased and of N-cadherin, MM P-2 and MMP-9 declined in HeLa cells with statistical differences (P0.05) compared to that of unprocessed group. Conclusions 6-gingerol can inhibit the proliferation of HPV-positive cervical cancer cells and cell invasion. The mechanism may be associated with the effect of 6-gingerol on influencing the expression of epithelial-mesenchymal transition-related proteins.

Effect of Zhenwu Decoction on chronic heart failure rats based on RAAS/NF-κB/ inflammatory factor cascade reaction / 中草药

Objective: To investigate the therapeutic effect and potential mechanism of Zhenwu Decoction (ZWD) on chronic heart failure (CHF) rats. Methods: HPLC fingerprint of ZWD was established. All male SD rats were randomly divided into the sham operation group, the model group, the low, medium and high dose ZWD group (2.187 5, 4.375, and 8.75 g/kg) and the captopril group (10 mg/kg). Except for the sham operation group, the rest of rats were all established into the CHF model rats by ligating the left anterior descending branch of the coronary artery, after 8 weeks, all rats were ig administration for 4 weeks. The hemodynamic, viscera index, HE dyeing test were conducted at the end of experiments. Serum angiotensin II (Ang II), aldosterone (ALD), nuclear factor kappa B (NF-κB), amino terminal brain natriuretic peptide (NT-proBNP), tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6) were determinated by ELISA, and myocardial NF-κB protein expression was detected by Western blotting. Results: Higenamine, paeoniflorin, atractylenolide III, 6-gingerol and dehydrotumulosic acid, the five constituents of Zhenwu Decoction, were identified by HPLC chart. Compared with the model group, the administration of the ZWD significantly improved the hemodynamic parameters (P < 0.05), reduced the organ index (P < 0.05) and improved myocardial injury, reduced the serum Ang II, ALD, NF-κB, NT-proBNP, TNF-α and IL-6 levels and the myocardial NF-κB protein expression (P < 0.05). Conclusion: HPLC results provided an evidence for the quality control and pharmacodynamic substance of ZWD. ZWD can ameliorate CHF, which may be related to the inhibition of renin- angiotensin-aldosterone system (RAAS)/NF-κB/inflammatory factor cascade reaction.

HPLC-ELSD fingerprint of Zhenwu Decoction and simultaneous determination of 13 components / 中草药

Objective: To establish HPLC-ELSD fingerprint of Zhenwu Decoction(ZWD), screen out the signature components of ZWD through chemical pattern recognition, so as to establish the content determination method of ZWD based on this index. Methods: The fingerprint of 16 batches of ZWD was established by HPLC-ELSD method. The similarity evaluation system of traditional Chinese medicine chromatographic fingerprint (2012 Version) was used for similarity evaluation to determine the common peaks and its attribution. Cluster analysis (CA), principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) were used to select the index components of ZWD. Results: The fingerprint of ZWD was established, 38 common peaks were confirmed, and the similarity was > 0.95. The results of CA, PCA and OPLS-DA were consistent and the samples were divided into three categories. Benzoylmesaconine, benzoylaconitine, benzoylhypacoitine, polyporenic acid C, pachymic acid, atractylenolide II, atractylenolide III, oxypaeoniflorin, albiflorin, paeoniflorin and benzoylpaeoniflorin were identified as the 11 index components with significant difference contribution in different batches of ZWD samples. 6-Gingerol and 6-shogaol were the main active components of ginger, so the above 13 components were taken as the index components of ZWD. The chromatographic peak separation degree and linear relationship were good. The average recovery rate was 96.46%-99.80%, RSD ≤ 3.15%. The mass fraction range of benzoylmesaconine, benzoylaconitine, benzoylhypacoitine, polyporenic acid C, pachymic acid, atractylenolide II, atractylenolide III, oxypaeoniflorin, albiflorin, paeoniflorin, benzoylpaeoniflorin, 6-gingerol, 6-shogaol in 16 batches were 283.93-576.86, 25.05-147.39, 62.96-303.37, 31.24-131.27, 9.76-44.04, 32.15-83.55, 76.55-333.13, 17.48-146.61, 456.58-1554.14, 3 322.48-5 590.01, 158.21-556.50, 525.85-582.92 and 68.52-74.73 mg/g, respectively. Conclusion: The fingerprint combined with PCA, CA and OPLS-DA can comprehensively evaluate the quality of ZWD. This method is stable and reliable, providing reference for the quality evaluation.

Effect of different decocting methods on active ingredients in Banxia Xiexin Decoction / 中草药

Objective To investigate the effects of the three methods of decocting with deslag, decocting without deslag, and double decocting on the content of nine ingredients baicalin, baicalein, ginsenoside Re, ginsenoside Rb1, monoammonium glycyrrhizinate hydrate, liquiritin, 6-gingerol, berberine hydrochloride, palmatine hydrochloride, and total flavonoids in Banxia Xiexin Decoction (BXD). Methods Nine index components were determined by HPLC. The HPLC analysis was performed on Welch Ultimate XB-C18 column (250 mm × 4.6 mm, 5 μm) with mobile phase of acetonitrile-0.1% phosphate aqueous solution for gradient elution; And carried out at column temperature of 28 ℃, volume flow of 0.9 mL/min, and detection wavelength of 203, 252, 280, and 355 nm. The total flavonoids were determined by colorimetry. Results Nine kinds of ingredients and total flavonoids could be detected in three different decoctions. In the method of decocting with deslag, baicalin, baicalein, ginsenoside Rb1, monoammonium glycyrrhizinate hydrate, and liquiritin increased by 10.01%, 12.88%, 29.09%, 16.75%, and 15.02%, respectively, compared with decocting without deslag; It decreased by 5.54%, 4.15%, 14.49%, 7.85%, and 9.18%, respectively compared with double decocting; Ginsenoside Re, 6-gingerol, berberine hydrochloride, and palmatine hydrochloride increased by 37.90%, 3.78%, 5.33%, and 5.99% compared with decocting without deslag, respectively; compared to the double decocting methods, it increased by 1.07%, 11.57%, 3.41%, and 1.93%. The total flavonoids increased 22.61% higher than decocting without deslag and 6.54% higher than double decocting. Conclusion: The results can effectively reflect the quality difference of different decocting methods. Among the three methods of decoction, the method of decocting without deslag has significantly improved the dissolution of the active ingredients of each component in the decoction, and improve the clinical efficacy of BXD to a certain extent. It provides a good experimental basis for the decocting without deslag method used in Zhang Zhongjing’s Treatise on Febrile Diseases.

Study on efficacy network of Chaihu Guizhi Ganjiang Decoction in treating insomnia / 中草药

Objective: To investigate the mechanisms of effects of Chaihu Guizhi Ganjiang Decoction in the treatment of insomnia by using network pharmacology methods. Methods: TCMSP and TCMID were used to lock the targets of seven herbs in Chaihu Guizhi Ganjiang Decoction. TTD, DrugBank, and PubMed were used to search targets of insomnia and construct a “disease-prescription-target” network. STRING and Cytoscape were used to perform enrichment analysis and clarify the mechanism of core targets in the network. Results: The PPI network of Chaihu Guizhi Ganjiang Decoction contained 640 targets and the PPI network of insomnia included 175 targets. A total of 29 core targets and 80 interactions were found after enrichment analysis between two PPI networks. After GO enrichment analysis and KEGG pathway analysis of 29 key targets, we found that 171 active ingredients in Chaihu Guizhi Ganjiang Decoction such as saikosaponin a, saikosaponin d, quercetin, calcium carbonate, 6-gingerol, kaempferol, and wogonin, which played a role in the treatment of insomnia mainly through 29 core targets such as CACNA1C, GABRA1, GABRA2, GABRB3, GABRA3, with biological processes such as target and synaptic signaling, regulation of membrane potential, G-protein coupled receptor signaling pathway, and molecular functions such as neurotransmitter receptor activity, ion-gated channel activity, GABA-A receptor activity, and functional pathways composed by plasmalemma, synapse, and other cells such as neural active ligand-receptor interaction, retrograde endogenous cannabinoid signal transduction, and serotoninergic synapses. Conclusion: The pharmacological substance basis for the treatment of insomnia was composed of 171 active ingredients such as saikosaponin a and saikosaponin d. The efficacy network of “soothing liver and invigorating spleen, regulating yin and yang” was constituted by several pathways like the neural active ligand-receptor interaction and 29 targets such as CACNA1C. Our results provide network pharmacological evidence for clinical rational use of Chaihu Guizhi Ganjiang Decoction for insomnia.

Quality Evaluation of Standard Decoction of Zingiberis Rhizoma / 中国实验方剂学杂志

Objective: To establish the quality control methods for the standard decoction of Zingiberis Rhizoma. Method: DNA barcode primitives were identified for the medicinal materials from different origins; according to the standard of Chinese herbal medicine decoction preparation principle,the identified Zingiberis Rhizoma was prepared into standard decoction for analysis. Meanwhile, the extraction method and analysis method were validated from methodologies, and the transfer rate of 6-gingerol as well as the extraction rate of standard decoction of Zingiberis Rhizoma were calculated. In addition,the quality standard of standard decoction of Zingiberis Rhizoma was also established based. The structures of main chromatographic peaks were identified by ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) to clarify the main chemical constituents in the standard decoction of Zingiberis Rhizoma. Result: All the samples were identified as Zingiberis Rhizoma. Under the conditions established in this paper,the standard curve of 6-gingerol was Y=661.56X+2.493 3(r=0.999 3),and the RSD was 0.5%in precision test, indicating that the instrument precision was good. The repeatability test showed that the RSD was 0.3%, indicating that the method had good repeatability. The stability test showed that the RSD was 0.4%, indicating that the test solution had good stability within 24 h. The recovery rate was 97.2%and the RSD was 0.6%,indicating that the method was accurate and reliable. 6-gingerol's transfer rate ranged from 31.8%to 57.4%and the extraction rate was within the range of 9.6%-23.1%. The fingerprint similarity of 12 batches of Zingiberis Rhizoma standard decoction was>90%. Conclusion: The established quality control method for Zingiberis Rhizoma was stable and feasible; meanwhile, the standard preparation method for Zingiberis Rhizoma and its quality evaluation system were also established in this study.

Longevity and Stress Resistant Property of 6-Gingerol from Zingiber officinale Roscoe in Caenorhabditis elegans

In order to discover lifespan-extending compounds made from natural resources, activity-guided fractionation of Zingiber officinale Roscoe (Zingiberaceae) ethanol extract was performed using the Caenorhabditis elegans (C. elegans) model system. The compound 6-gingerol was isolated from the most active ethyl acetate soluble fraction, and showed potent longevity-promoting activity. It also elevated the survival rate of worms against stressful environment including thermal, osmotic, and oxidative conditions. Additionally, 6-gingerol elevated the antioxidant enzyme activities of C. elegans, and showed a dose-depend reduction of intracellular reactive oxygen species (ROS) accumulation in worms. Further studies demonstrated that the increased stress tolerance of 6-gingerol-mediated worms could result from the promotion of stress resistance proteins such as heat shock protein (HSP-16.2) and superoxide dismutase (SOD-3). The lipofuscin levels in 6-gingerol treated intestinal worms were decreased in comparison to the control group. No significant 6-gingerol-related changes, including growth, food intake, reproduction, and movement were noted. These results suggest that 6-gingerol exerted longevity-promoting activities independently of these factors and could extend the human lifespan.

Difference of chemical constituents and efficacy between crude and processed Pinelliae Rhizoma / 中草药

Objective To study the chemical constituents and effects of crude and processed Pinelliae Rhizoma. Methods The contents of inosine, guanosine, adenosine, succinic acid, ephedrine hydrochloride, liquiritin, glyeyrrhizie acid, and 6-gingerol of Pinelliae Rhizoma, Pinelliae Rhizoma Praeparatum cum Alumine, Pinelliae Rhizoma Praeparatum cum Zingibere et Alumine, and Pinelliae Rhizoma Praeparatum were detected by HPLC. The pharmacodynamics of the traditional efficacy of expectorant and cough relieving was studied by stimulating mice with phenol red and concentrated ammonia in the trachea of mice. Results The contents of inosine, guanosine, adenosine, succinic acid, and ephedrine hydrochloride decreased significantly after processing, and inosine was not detected in Pinelliae Rhizoma Praeparatum cum Alumine. Compared with the three processed products, the content of inosine, guanosine, adenosine and succinic acid was the highest in the Pinelliae Rhizoma Praeparatum cum Alumine, the lowest was in Pinelliae Rhizoma Praeparatum cum Zingibere et Alumine, and in consistent with the effect of resolving phlegm. The four components were the active components of resolving phlegm effect. Adding alumen during Pinelliae Rhizoma Praeparatum cum Alumine processing has also enhanced its effectiveness. Pinelliae Rhizoma Praeparatum has the strongest antitussive effect, followed by Pinelliae Rhizoma, Pinelliae Rhizoma Praeparatum cum Alumine and Pinelliae Rhizoma Praeparatum cum Zingibere et Alumine. Adding licorice and lime water during Pinelliae Rhizoma Praeparatum processing, licorice (peak 6: liquiritin, peak 7: ammonium glycyrrhizinate) had a powerful antitussive effect and enhanced its antitussive effect. After processing by ginger and white peony, ginger (peak 8: 6-gingerol) is good at warming middle energizer to arrest vomiting, thus enhance antiemetic effect and weaken phlegm, cough effect of Pinelliae Rhizoma Praeparatum cum Zingibere et Alumine. Conclusion The chemical composition and efficacy of Pinelliae Rhizoma have changed after being processed, and different processing methods have different effects on its chemical composition and efficacy.

Drying processing method for Zingiberis Rhizoma based on multiple bioactive constituents / 中草药

Objective To compare the effects of different drying methods on six bioactive constituents of Zingiberis Rhizoma (ZR), and explore the dynamic changes of bioactive constituents and water content during the drying process. Methods The multiple components in ZR were simultaneously measured by HPLC, and 6-gingerol, 8-gingerol, 10-gingerol, 6-shogaol, α-curcumene, (E)- β-farnesene were used as indexes to evaluate ZR obtained from different drying methods. The Weibull function was used to simulate the dynamic change of water content, which was combined with the dynamic changes of components during the drying process of ZR to explore the principle of drying process. Results A total of 12 kinds of drying methods had a certain effect on the multiple components of ZR, and the components presented the fluctuation change in the drying process. The coefficient of correlation of Weibull functional simulation of ZR drying process was greater than 0.990. Conclusion ZR obtained by drying at 60 ℃ was better. Water content range of 6%-15% was suitable for processing ZR. 6-gingerol, 8-gingerol, 10-gingerol, and 6-shogaol were significantly negatively correlated with the moisture content of ZR. The Weibull distribution model could well simulate the fluctuation change of water content in the drying process, and it was of great significance for the prediction and quality control of ZR during drying process, which could also provide a technical basis for the use of modern drying technology to dry ZR at the same time.

Effect of azone on transdermal absorption of 6-gingerol / 中成药

AIM To study the effect of azone on transdermal absorption of 6-gingerol.METHODS In vitro transdermal diffusion test was performed by TP-6 horizontal diffusion pool.In vitro rat skins were selected as permeation barrier,the effects of different concentrations of ethanol and azone on permeation performance of 6-gingerol were investigated.RESULTS Both 30％ ethanol and 3％ azone contributed to the significant permeation enhancement of 6-gingerol.CONCLUSION This research can provide reference for the preparation of transdermal drug delivery systems containing 6-gingerol.

10-gingerol inhibits proliferation of hepatocellular carcinoma HepG2 cells via Src/STAT3 signaling pathway / 南方医科大学学报

<p><b>OBJECTIVE</b>To study the inhibitory effect of 10-gingerol on the proliferation of hepatocellular carcinoma HepG2 cells and the role of Src/STAT3 signaling pathway in mediating the effect.</p><p><b>METHODS</b>SYBYL-X2.1 software was used to simulate the interaction between 10-gingerol and Src. HepG2 cells treated with 10-gingerol at 1, 3, 10 or μol/L for 24 h were assessed for cell viability using MTT assay, and EdU staining was used to detect the cell proliferation and calculate the number of positive cells. The expressions of p-Src and p-STAT3 were detected using Western blotting, and the mRNA expressions of the target genes of STAT3 (cyclin D1 and CMCC) were detected using qPCR.</p><p><b>RESULTS</b>10-gingerol was capable of forming hydrogen bond with such Src residues as TRY-340, MET-341, MET-314, ASP-404, and ILE-336. MTT assay showed that 10-gingerol at 3 and 10 μmol/L significantly lowered the viability of HepG2 cells ( < 0.001). Treatment with 1, 3, and 10 μmol/L 10-gingerol significantly reduces the number of EdU-positive HepG 2 cells ( < 0.001). Western blotting showed that 10-gingerol at 3 and 10 μmol/L significantly decreased the phosphorylation levels of Src and STAT3 in HepG2 cells ( < 0.01). 10-gingerol at 1, 3, and 10 μmol/L significantly decreased the mRNA expressions of cyclin D1 and CMCC as shown by qPCR ( < 0.01).</p><p><b>CONCLUSIONS</b>10-gingerol can dose-dependently inhibit the proliferation of HepG2 cells and suppress the activation of Src and STAT3.</p>

6-Gingerol inhibits hair cycle via induction of MMP2 and MMP9 expression

ABSTRACT 6-Gingerol is the major active constituent of ginger. In the current study, we aimed to investigate the mechanisms underlying the effects of 6-Gingerol on hair growth. Mice were randomly divided into five groups; after hair depilation (day 0), mice were treated with saline, or different concentrations of 6-Gingerol for 11 days. The histomorphological characteristics of the growing hair follicles were examined after hematoxylin and eosin staining. The results indicated that 6-Gingerol significantly suppressed hair growth compared with that in the control group. And choose the concentration of 6-Gingerol at 1 mg/mL to treated with mice. Moreover, 6-Gingerol (1 mg/mL) significantly reduced hair re-growth ratio, hair follicle number, and hair follicle length, which were associated with increased expression of MMP2 and MMP9. Furthermore, the growth factors, such as EGF, KGF, VEGF, IGF-1 and TGF-β participate in the hair follicle cycle regulation and regulate hair growth. We then measured the concentrations of them using ELISA assays, and the results showed that 6-Gingerol decreased EGF, KGF, VEGF, and IGF-1 concentrations, and increased TGF-β concentration. Thus, this study showed that 6-Gingerol might act as a hair growth suppressive drug via induction of MMP2 and MMP9 expression, which could interfere with the hair cycle.