Study on the Synthesis,Structural Characterization and Activity of Fluorine-Containing Borneol Ester / 广州中医药大学学报

Objective Four fluorine-containing borneol ester were synthesized and analyzed for structure characterization and activity.Methods Four fluorine-containing borneol ester derivatives were synthesized by the reaction of fluorinated carboxylic acid and borneol by using p-toluenesulfonic acid as catalyst,and the structures of borneol esters were characterized by 1HNMR and 13CNMR.Molecular docking of the four fluorine-containing borneol ester with P-glycoprotein was carried out by Autodock Vina software.Results Four fluorine-containing borneol ester,bornyl 2-chloro-4-trifluoromethyl benzoate,bornyl 2-chloro-5-fluoro benzoate,bornyl 2-chloro-5-trifluoromethyl benzoate,bornyl 3-trifluoromethyl benzoate,were synthesized.The structures of the borneol ester were confirmed by 1HNMR and 13CNMR.4 fluorine-containing borneol ester had good binding ability with P-glycoprotein.Conclusion Four borneol ester compounds were synthesized,and the borneol ester enriched the types of borneol derivatives,which is of reference value for expanding the application range of borneol.

Borneol attenuates inflammation and inhibits cardiac remodeling after myocardial infarction in mice via TRPM8 / 中国病理生理杂志

AIM:To examine the effects of borneol on inflammation and myocardial remodeling after myocar-dial infarction(MI)in mice,and to investigate the underlying mechanisms.METHODS:Eight-week-old wild-type(WT)C57BL/6 mice and transient receptor potential cation channel subfamily M member 8(TRPM8)gene knockout(TRPM8-/-)mice were randomly divided into sham and MI groups,and were subsequently treated with normal saline(control group)or borneol(borneol group)via gavage.Survival curves were plotted for WT and TRPM8-/-mice with MI treated with or with-out borneol.After 28 d,cardiac function of the mice was assessed through echocardiography,and haemodynamic indexes were evaluated using a multi-channel physiological instrument.Infarct size,myocardial hypertrophy and interstitial fibro-sis were assessed via pathological staining.In addition,inflammatory response in the peri-infarct region was detected.RE-SULTS:The TRPM8 expression was up-regulated in the peri-infarct region of the mice with MI(P＜0.05),and borneol had no effect on TRPM8 expression(P＞0.05).Borneol increased the survival rate,reduced the infarct size,inhibited car-diac remodeling and improved cardiac function in WT mice with MI(P＜0.05 or P＜0.01).However,it did not affect the survival rate,infarct size,myocardial hypertrophy,myocardial fibrosis or cardiac function in TRPM8-/-mice(P＞0.05).Furthermore,borneol reduced inflammatory cell infiltration and the expression of inflammatory cytokines,tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β),IL-6 and monocyte chemotactic protein-1(MCP-1),in WT mice(P＜0.05 or P＜0.01)but not in TRPM8-/-mice(P＞0.05).CONCLUSION:Borneol attenuates inflammation,inhibits cardiac re-modeling and improves cardiac function in mice with MI via TRPM8.

Design, synthesis and biological activity evaluation of water-soluble borneol phosphate prodrug / 中国药科大学学报

@#Abstract: In this study, structural optimization of borneol was carried out to improve their solubility and promote their further application in stroke therapy. BP-3, a prodrug of borneol, was designed and synthesized based on the principle of phosphate modification. The solubility of BP-3 was determined by evaporative light scattering detector (ELSD), and the degree and speed of drug release were tested in mouse plasma, and the neuroprotective effect of BP-3 was evaluated in mouse model of transient middle cerebral artery occlusion (tMCAO). According to the results, BP-3 was completely soluble in saline at 20 mg/mL; in mouse plasma, approximately 40% of the borneol were released within 2 h; in the tMCAO mouse model, TTC staining showed that BP-3 was effective in reducing the infarct area; Nissl staining showed that BP-3 ameliorated the neuronal injury; the grip and grasping strength tests elucidated that BP-3 reduced the damage of sports ability caused by injury; and the rotating rod test proved that BP-3 could promote the recovery of motor ability in mice. BP-3 has good water solubility, suitable drug release rate and excellent neuroprotective effects, and has broad prospects for drug development.

Systematic identification of chemical forms of key terpene synthase in Cinnamomum camphora / 中国中药杂志

Cinnamomum camphora is an important economic tree species in China. According to the type and content of main components in the volatile oil of leaf, C. camphora were divided into five chemotypes, including borneol-type, camphor-type, linalool-type, cineole-type, and nerolidol-type. Terpene synthase(TPS) is the key enzyme for the formation of these compounds. Although several key enzyme genes have been identified, the biosynthetic pathway of(+)-borneol, which has the most economic value, has not been reported. In this study, nine terpenoid synthase genes CcTPS1-CcTPS9 were cloned through transcriptome analysis of four chemical-type leaves. After the recombinant protein was induced by Escherichia coli, geranyl pyrophosphate(GPP) and farnesyl pyrophosphate(FPP) were used as substrates for enzymatic reaction, respectively. Both CcTPS1 and CcTPS9 could catalyze GPP to produce bornyl pyrophosphate, which could be hydrolyzed by phosphohydrolase to obtain(+)-borneol, and the product of(+)-borneol accounted for 0.4% and 89.3%, respectively. Both CcTPS3 and CcTPS6 could catalyze GPP to generate a single product linalool, and CcTPS6 could also react with FPP to generate nerolidol. CcTPS8 reacted with GPP to produce 1,8-cineol(30.71%). Nine terpene synthases produced 9 monoterpene and 6 sesquiterpenes. The study has identified the key enzyme genes responsible for borneol biosynthesis in C. camphora for the first time, laying a foundation for further elucidating the molecular mechanism of chemical type formation and cultivating new varieties of borneol with high yield by using bioengineering technology.

Protective effects of three kinds of borneol on different brain regions in acute cerebral ischemia/reperfusion model rats / 中国中药杂志

This study compared the ameliorating effects of L-borneol, natural borneol, and synthetic borneol on the injury of different brain regions in the rat model of acute phase of cerebral ischemia/reperfusion(I/R) for the first time, which provides a reference for guiding the rational application of borneol in the early treatment of ischemic stroke and has important academic and application values. Healthy specific pathogen-free(SPF)-grade SD male rats were randomly assigned into 13 groups: a sham-operation group, a model group, a Tween model group, a positive drug(nimodipine) group, and high-, medium-, and low-dose(0.2, 0.1, and 0.05 g·kg~(-1), respectively) groups of L-borneol, natural borneol, and synthetic borneol according to body weight. After 3 days of pre-administration, the rat model of I/R was established by suture-occluded method and confirmed by laser speckle imaging. The corresponding agents in different groups were then administered for 1 day. The body temperature was monitored regularly before pre-administration, days 1, 2, and 3 of pre-administration, 2 h after model awakening, and 1 d after model establishment. Neurological function was evaluated based on Zea-Longa score and modified neurological severity score(mNSS) 2 h and next day after awakening. The rats were anesthetized 30 min after the last administration, and blood was collected from the abdominal aorta. Enzyme-linked immunoassay assay(ELISA) was employed to determine the serum levels of tumor necrosis factor-alpha(TNF-α), interleukin-6(IL-6), IL-4, and transforming growth factor-beta1(TGF-β1). The brain tissues were stained with triphenyltetrazolium chloride(TTC) for the calculation of cerebral infarction rate, and hematoxylin-eosin(HE) staining was used for observing and semi-quantitatively evaluating the pathological damage in different brain regions. Immunohistochemistry was employed to detect the expression of ionized calcium binding adapter molecule 1(IBA1) in microglia. q-PCR was carried out to determine the mRNA levels of iNOS and arginase 1(Arg1), markers of polarization phenotype M1 and M2 in microglia. Compared with the sham-operation group, the model group and the Tween model group showed significantly elevated body temperature, Zea-Longa score, mNSS, and cerebral infarction rate, severely damaged cortex, hippocampus, and striatum, increased serum levels of IL-6 and TNF-α, and decreased serum levels of IL-4 and TGF-β1. The three borneol products had a tendency to reduce the body temperature of rats 1 day after modeling. Synthetic borneol at the doses of 0.2 and 0.05 g·kg~(-1), as well as L-borneol of 0.1 g·kg~(-1), significantly reduced Zea-Longa score and mNSS. The three borneol products at the dose of 0.2 g·kg~(-1) significantly reduced the cerebral infarction rate. L-borneol at the doses of 0.2 and 0.1 g·kg~(-1) and natural borneol at the dose of 0.1 g·kg~(-1) significantly reduced the pathological damage of the cortex. L-borneol and natural borneol at the dose of 0.1 g·kg~(-1) attenuated the pathological damage of hippocampus, and 0.2 g·kg~(-1) L-borneol attenuated the damage of striatum. The 0.2 g·kg~(-1) L-borneol and the three doses of natural borneol and synthetic borneol significantly reduced the serum level of TNF-α, and the 0.1 g·kg~(-1) synthetic borneol reduced the level of IL-6. L-borneol and synthetic borneol at the dose of 0.2 g·kg~(-1) significantly inhibited the activation of cortical microglia, and 0.2 g·kg~(-1) L-borneol up-regulated the expression of Arg1 and down-regulated the expression level of iNOS. In conclusion, the three borneol products may alleviate inflammation to ameliorate the pathological damage of brain regions of rats in the acute phase of I/R by inhibiting the activation of microglia and promoting the polarization of microglia from M1 type to M2 type. The protective effect on brain followed a trend of L-borneol > synthetic borneol > natural borneol. We suggest L-borneol the first choice for the treatment of I/R in the acute phase.

Advances in preclinical studies on borneol as an adjuvant for glioma / 药学实践与服务

Glioma is a common primary malignant brain tumor. At present, the main clinical treatment is surgical resection combined with radiotherapy and chemotherapy. Due to the selective permeability of the blood-brain barrier and the characteristics of multi-drug resistance of tumor cells, the therapeutic effect is not ideal. In recent years, studies have found that borneol could open the blood-brain barrier and promote the infiltration of chemotherapy drugs. When borneol is combined with or co-carried with chemotherapy drugs, chemotherapy drugs could target more glioma tissues and increase efficacy. The preclinical studies on the combination of borneol and chemotherapy drugs in recent years were reviewed in this article, in order to provide useful reference for the treatment of glioma.

Determination of camphor residue and borneol content in Qingchang suppository by GC / 药学实践与服务

Objective To establish a gas chromatography for simultaneous determination of camphor residue and borneolum content in Qingchang Suppository. Methods Gas chromatograph method was used. The chromatographic column was Agilent capillary column(30 m×0.25 mm×0.25 µm). The column temperature was 140 ℃. The sample injection temperature was 250 ℃. The FID detector temperature was 250 ℃. Results Camphor，borneol and isoborneol content showed good linear in the extent of 0.0299~1.497(r=1.000), 0.0205~1.025(r=1.000), 0.0097~0.4830 µg (r=1.000). RSDs of precision，stability and repeatability test results were less than 2%. The recovery was 99.7%, 101.0%, 102.5%. Conclusion This method is simple and quick with accurate result, which could be used for the content determination of Borneol in Qingchang Suppository.

In Vitro Cultured Calculus Bovis Combined with Borneol Activates PI3K/Akt Pathway and Inhibit Neuronal Apoptosis in Cerebral Ischemia-Reperfusion Model Rats / 华中科技大学学报(医学版)

Objective Based on PI3K/Akt signaling pathway,the molecular mechanism of brain protective effect of in vitro cultured Calculus Bovis(ICCB),borneol and their combination on cerebral ischemia-reperfusion model rats was discussed from the perspective of anti-apoptosis.Methods The model of transient middle cerebral artery occlusion(MCAO)was established by modified suture and reperfusion 90 minutes after ischemia.HE staining and Tunel staining were used to observe the pathological injury of brain tissue and the apoptosis of cerebral cortical neurons.The expression levels of PI3K/Akt pathway related proteins were detected by Western blotting and immunohistochemistry.Expression of mRNA was detected by RT-PCR.Results Com-pared with the solvent model group,the pathological injury of brain tissue was reduced and apoptosis of cortical neurons on the ischemic side was inhibited;the expressions of p-PI3K,p-Akt and Bcl-2 protein in the ischemic brain tissue were increased;the expression of Caspase-3,Bax protein and Bax/Bcl-2 were decreased in ICCB group,borneol group and combination group.Conclusion The brain protective effect of ICCB,borneol and their combination is related to activation of PI3K/Akt path-way and inhibition of neuronal apoptosis after cerebral ischemia-reperfusion,so as to play the role of"opening the orifices and waking the mind".

Sensitizing effect of d-borneol on cisplatin-resistant NSCLC based on transcriptomics and its mechanism / 中国药理学通报

Aim To explore the key targets of d-borneol combined with eisplatin for sensitization of cisplatin-resistant NCSLC cells by RNA-Seq and verify its mechanism. Methods Cisplatin-resistant human large cell lung cancer cells (H460/CDDP) were inoculated into the right armpit of male BALB/c nude mice (4 weeks old) to construct a xenograft tumor model. Then they were randomly divided into control group, vehicle group, eisplatin group, and combination group (d-borneol + eisplatin) with 6 nude mice and treated for 14 d. After last administration of 24 h, the tumor tissue was taken for RNA-Seq. And then real-time reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry (IHC) were used to verify the expression of cell cycle-related molecules. Results RNA-seq analysis showed that there were significant differences in gene expression between the eisplatin group and combined group, and they were significantly enriched in cell cycle. RT-PCR and IHC results showed that d-borneol combined with eisplatin could significantly inhibit the expressions of cyclins (cyclin A2, cyclin D3) and cyclin-dependent kinases (CDK2, CDK6) and promote the expression of its upstream molecular cyclin-dependent kinase inhibitor CD-KI (P21, P27) (P<0. 05, P<0.01). Conclusions d-Borneol increases the sensitivity of eisplatin by increasing the expression of P21 and P27 and inhibiting the expression of cyclinA2/D3 and CDK2/6 to induce cell cycle arrest and inhibit the malignant proliferation of H460/CDDP cells, thereby achieving the effect of anti-drug sensitization.

Protective effect of borneol on the cutaneous toxicity of gilteritinib / 浙江大学学报·医学版

OBJECTIVES@#To investigate the effect of borneol on cutaneous toxicity of gilteritinib and to explore possible compounds that can intervene with the cutaneous toxicity.@*METHODS@#C57BL/6J male mice were given gilteritinib by continuous gavage for 28 d and the damage to keratinocytes in the skin tissues was observed with hematoxylin and eosin (HE) staining, TUNEL assay and immunohistochemistry. Human keratinocytes HaCaT were treated with gilteritinib, and cell death and morphological changes were examined by SRB staining and microscopy; apoptosis of HaCaT cells was examined by Western blotting, flow cytometry with propidium iodide/AnnexinⅤ double staining and immunofluorescence; the accumulation of cellular reactive oxygen species (ROS) was examined by flow cytometry with DCFH-DA. Compounds that can effectively intervene the cutaneous toxicity of gilteritinib were screened from a natural compound library using SRB method, and the intervention effect of borneol on gilteritinib cutaneous toxicity was further investigated in HaCaT cells and C57BL/6J male mice.@*RESULTS@#In vivo studies showed pathological changes in the skin with apoptosis of keratinocytes in the stratum spinosum and stratum granulosum in the modeling group. Invitro studies showed apoptosis of HaCaT cells, significant up-regulation of cleaved poly (ADP-ribose) polymerase (c-PARP) and gamma-H2A histone family member X (γ-H2AX) levels, and increased accumulation of ROS in gilteritinib-modeled skin keratinocytes compared with controls. Screening of the natural compound library revealed that borneol showed excellent intervention effects on the death of HaCaT cells. In vitro, cell apoptosis was significantly reduced in the borneol+gilteritinib group compared to the gilteritinib control group. The levels of c-PARP, γ-H2AX and ROS in cells were significantly decreased. In vivo, borneol alleviated gilteritinib-induced skin pathological changes and skin cell apoptosis in mice.@*CONCLUSIONS@#Gilteritinib induces keratinocytes apoptosis by causing intracellular ROS accumulation, resulting in cutaneous toxicity. Borneol can ameliorate the cutaneous toxicity of gilteritinib by reducing the accumulation of ROS and apoptosis of keratinocytes in the skin tissue.

Study on the mechanism of "guiding action" of borneol in Suxiaojiuxin pills / 药学学报

In order to research the mechanism of guiding action of borneol in Suxiaojiuxin pills, the model of in vitro intestinal absorption, in vivo drug metabolism of mice and cell in vitro absorption model of Caco-2 were established firstly. All animal experiments were in accordance with the regulations of the Animal Ethics Committee of Nankai University. The results showed that the cumulative absorption quantity and absorption permeability of ferulic acid and ligustilide in the intestinal juice of Suxiaojiuxin pills group were significantly increased comparing with fake Suxiaojiuxin pills group, which don't contain borneol. By using borneol, the content of ferulic acid and ligustilide in the blood and tissues, such as heart, were added. The transepithelial resistance value and the content of horseradish peroxidase (HRP) in Caco-2 were rapidly decreased and increased, respectively. Due to further explore mechanism of promoting intestinal absorption of borneol for drugs, in this study, photosensitive probes of borneol were synthesized to capture its targets, and dual luciferase reporter system was used to evaluate its activity of calcium. It was found that it could make calcium overload by regulating transient receptor potential cation channel, subfamily M, member 8 (TrpM8). Then, the results of mass spectrometry imaging showed that the accumulation of ferulic acid in the heart was significantly increased by borneol, and the relaxation rate of rat thoracic aorta was enhanced obviously. In summary, the borneol in Suxiaojiuxin pills can expand cell space and increase intestinal permeability by acting on TrpM8, thus promoting the intestinal absorption, tissue distribution and target organ enrichment of drugs.

The anti-glioma effects of borneol and RGD co-modified docetaxel loaded nanoparticles after intranasal administration / 药学学报

Borneol (Bo) and Arg-Gly-Asp (RGD) co-modified docetaxel (DTX) loaded MPEG-PLGA nanoparticles (DTX-Bo-RGD-NPs) were prepared to improve the therapeutic effect of DTX against glioma after intranasal administration. DTX-Bo-RGD-NPs were prepared by emulsification-solvent evaporation method, and their morphology, particle size, zeta potential, drug loading capacity (DLC), stability, and in vitro release properties were investigated. The fluorescence probe coumarin-6 loaded NPs were prepared for investigating the NPs' uptake property on C6 and 16HBE cell models to evaluate in vitro targeting ability. The DiR loaded NPs were prepared for observing the fluorescence intensity at the brain tumor site after intranasal administration through in vivo imaging system in a C6 rat orthotropic model, evaluating the targeting ability in vivo. The anti-tumor effects of DTX-Bo-RGD-NPs were also investigated in such C6 rat orthotropic model in vivo. Animal welfare and experimental procedures are in compliance with the regulations of the Animal Ethics Committee of Shanghai University of Traditional Chinese Medicine. The results showed that DTX-Bo-RGD-NPs were spherical and uniformly distributed, with a particle size of about 140 nm and a zeta potential of -20 to -30 mV. The drug delivery system showed good stability and sustained release property in vitro, and favorable brain tumor targeting effect in vitro and in vivo. Such novel drug delivery system significantly improved the accumulation of DTX-Bo-RGD-NPs in tumor sites and displayed a higher brain tumor targeting efficiency, providing promising therapeutics of DTX for the treatment of glioma after intranasal administration.

Literature study on herbal medicine of Borneol / 国际中医中药杂志

As a collective noun of incense and medicine, fragrant medicine has long been integrated into Chinese culture. It is not only a symbol of the cultural exchange between China and foreign countries in the middle ancient times, but also plays a very important role in medicine and other fields. Among them, Borneol can not only be used for medicinal purposes, but also for incense and fumigation, as well as food, tea, wine and other applications. This paper intends to sort out the medicinal properties, effects and other applications of Borneol recorded in ancient books of traditional Chinese herbs in the past dynasties, focusing on summarizing its medicinal properties, meridians, effects, compatibility and application characteristics. In addition, modern pharmacological action was included as a supplement, in order to provide reference for the clinical use of Borneol in medicinal aspects.

The effects of borneol on the pharmacokinetics and brain distribution of tanshinone IIA, salvianolic acid B and ginsenoside Rg / 中国天然药物

Fufang Danshen preparation (FDP) is consisted of Salviae Miltiorrhizar Radix et Rhizoma (Danshen), Notoginseng Radix et Rhizoma (Sanqi) and Borneolum Syntheticum (borneol). FDP is usually used to treat myocardial ischemia hypoxia, cerebral ischemia and alzheimer's disease, etc. In the treatment of cerebrovascular diseases, borneol is usually used to promote the absorption and distribution of the bioactive components to proper organs, especially to the brain. The purpose of this study is investigating the effects of borneol on the pharmacokinetics and brain distribution of tanshinone IIA (TS IIA), salvianolic acid B (SAB) and ginsenoside Rg1 in FDP. Male healthy Sprague-Dawley (SD) rats were given Danshen extracts, Sanqi extracts (Panax notoginsengsaponins) or simultaneously administered Danshenextracts, Sanqi extracts and borneol. Plasma and brain samples were collected at different points in time. The concentration of TS IIA, SAB and Rg1 was determined by UPLC-MS/MS method. The main pharmacokinetics parameters of plasma and brain tissue were calculated by using Phoenix WinNolin 6.1 software. In comparison with Danshen and Sanqi alone, there were significant differences in pharmacokinetic parameters of TS IIA, SAB and Rg1, and the brain distribution of SAB and TS IIA when Danshen, Sanqi and borneol were administrated together. Borneol statistically significant shortened t

Research progress of natural borneol resources / 中国中药杂志

Natural borneol is an important traditional Chinese medicine herb with resuscitation-inducing, antipyretic and analgesic effects, and has been widely used in the fields of medicine, perfume and chemical industry. At present, natural borneol is short supply, with promising market development prospects. This paper summarized the distribution of borneol plant resources, cultivation status and molecular biological research progress, in the expectation of providing basis and ideas for the research and application of natural borneol.

Cardioprotective Effect of Three Borneol Prevention and Administration on AMI Model Rats / 中国实验方剂学杂志

Objective::The effects of three different doses of borneol on acute myocardial infarction (AMI) model rats and the effects on oxidative stress factors were compared to provide reference for elucidation of the dose-effect relationship and mechanism of anti-myocardial infarction. Method::Healthy adult male SPF SD rats were randomly divided into sham operation group, model group, solvation model group, nitroglycerin group, Borneolum high, medium and low dose(0.6, 0.3, 0.15 g·kg-1) group, l-Borneolum and Borneolum syntheticum high, medium, low dose(0.2, 0.1, 0.05 g·kg-1) group, a total of 13 groups, 20 in each group. Gavage was performed at 20 mL·kg-1 once a day for 3 days of continuous preventive administration. The sham operation group and the model group were given the same volume of distilled water, and the solvation model group was given the same volume of 5% polysorbate 80.On the third day of the pre-administration, 30 minutes after the last dose, the left anterior descending coronary artery was ligated to make a model, and the successful rats were treated for 3 days. BL-420N biological system analyzer was used to record the ST-segment amplitude and hemodynamic changes. Rat body weight and cardiac weight were weighed to calculate cardiac viscera coefficients, 2, 3, 5-triphenyl tetrazolium chloride (TTC) staining was used to calculate the myocardial infarction rate. Hematoxylin-eosin (HE) staining was used to evaluate the degree of myocardial pathological damage. According to the kit requirements, serum levels of lactate dehydrogenase (LDH), aspartate amino-transaminase (AST), creatine kinase isoenzyme (CK-MB) and oxidative stress factors superoxide dismutase (SOD), malondialdehyde (MDA) were detected. Result::Compared with the sham operation group, the ST segment amplitude of the model group significantly increased after 5 minutes, the left ventricular diastolic blood pressure (LVDP) value increased significantly, and the measured maximum shortening velocity (Vpm) value of the left ventricular myocardial contraction component significantly decreased. The organ coefficient and myocardial infarction rate were extremely significantly increased, and the myocardial pathological tissue was severely damaged. The serum CK-MB, AST, LDH, and MDA contents were significantly increased (P<0.05, P<0.01). Compared with the solvation model group, the Borneolum and l-Borneolum in the middle and low, and the Borneolum syntheticum high dose groups could significantly inhibited the abnormal elevation of ST segments at different time points. The Borneolum and l-Borneolum high, medium, low, and Borneolum syntheticum high dose groups significantly increased the left ventricular systolic blood pressure (LVSP) value and decrease the LVDP value (P<0.01). The Borneolum medium, low, and l-Borneolum high, medium, Borneolum syntheticum high dose groups significantly increased the maximum rate of left ventricular pressure rise (dp/dt max) and Vpm value (P<0.05, P<0.01). The Borneolum and l-Borneolum medium, low dose groups significantly reduced rat cardiac organ coefficients. The Borneolum high, medium, low and l-Borneolum, Borneolum syntheticum medium, low dose groups significantly improved myocardial infarction in rats (P< 0.05, P<0.01). The Borneolum low, l-Borneolum high, medium, and Borneolum syntheticum high groups also significantly improved the degree of pathological damage (P<0.01). High dose of l-Borneolum significantly reduced CK-MB content, medium and low dose of l-Borneolum significantly reduced AST activity, medium and low dose of l-Borneolum, high, medium and low dose of Borneolum syntheticum significantly reduced LDH activity (P<0.05, P<0.01). Serum SOD activity of rats in l-Borneolum high, medium, and Borneolum syntheticum high dose groups increased significantly (P<0.05, P<0.01). Serum MDA levels in Borneolum high, medium, low, and l-Borneolum high, middle dose groups significantly decreased (P<0.01). Conclusion::Three kinds of borneol in different dose groups can play different degrees of myocardial protection. Under the experimental conditions, there was a trend of l-Borneolum>Borneolum>Borneolum syntheticum in improving the efficacy of myocardial infarction, the dose-effect of Borneolum was negatively correlated, Borneolum syntheticum was positively correlated, and no significant dose-effect relationship between l-Borneolum.

Pharmacokinetic studies of multi-bioactive components in rat plasma after oral administration of Xintiantai extract and effects of guide drug borneol on pharmacokinetics / 中草药·英文版

Objective: To investigate the in vivo pharmacokinetic characteristics of 17 bioactive components including ginsenoside Rg1, Rb1, Rd, berberine, epiberberine, jatrorrhizine, palmatine, columbamine, coptisine, evodiamine, dehydroevodiamine, rutaecarpine, limonin, hyperin, curcumin, demethoxycurcumin and bisdemethoxycurcumin in rat plasma after oral administration of Xintiantai I extract powder (XI) and Xintiantai I without guide drug borneol extract powder (XI without borneol), and study the compatibility effects of guide drug borneol on the pharmacokinetics. Methods: A UHPLC-MS/MS method was established and fully validated for the comparative pharmacokinetics of 17 bioactive components. The pharmacokinetics parameters of 17 bioactive components after oral administration of XI and XI without borneol were calculated by the software of DAS 3.0 and intercompared. Results: The specificity, linearity, lower limit of quantification (LLOQ), precision, accuracy, extraction recovery rates, matrix effects, and stability of the UHPLC-MS/MS assay were good within the acceptance criteria from FDA guidelines. Guide drug borneol can significantly increase AUC of G-Rd, palmatine, hyperin, curcumin, demethoxycurcumin, bisdemethoxycurcumin and Cmax of 16 bioactive components except for dehydroevodiamine (P < 0.05), decrease Tmax of G-Rd, berberine, columbamin, coptisine, limonin and MRT of 17 bioactive components in XI group (P < 0.05). Conclusion: Guide drug borneol enhanced the absorption of G-Rd, palmatine, hyperin, curcumin, demethoxycurcumin and bisdemethoxycurcumin.

Neuroprotective effect of borneol combined with astragaloside IV and Panax notoginseng saponins in cerebral ischemia reperfusion injury rat model through Notch signaling pathway / 中草药

Objective: To observe the neuroprotective effect of borneol combined with astragaloside IV (AST IV) and Panax notoginseng saponins (PNS) on cerebral ischemia reperfusion injury (CIRI) rat model through Notch signaling pathway. Methods: SD rats were randomly divided into sham group, model group, borneol (7.5 mg/kg) group, AST IV (25 mg/kg) group, PNS (10 mg/kg) group, AST IV (10 mg/kg) + PNS (25 mg/kg) group, borneol (7.5 mg/kg) + AST IV (25 mg/kg) + PNS (10 mg/kg) low dose group, borneol (15 mg/kg) + AST IV (20 mg/kg) + PNS (50 mg/kg) high dose group and edaravone (4 mg/kg) group. Rats in sham group and model group were ig 0.5% CMC-Na, edaravone group was ip drug, and the other groups were ig corresponding drugs, twice a day with an interval of 12 h. The right middle cerebral artery of rat was blocked by a suture method 2 h after last administration to establish a CIRI model. After 2 h of ischemia and 22 h of reperfusion, the eurological function scores were scored and pathological changes of ischemic cortex in brain tissues of rats were observed by HE staining. The expressions of neuron specific nuclear (NeuN) and endothelial barrier antigen (EBA) in ischemic cortex of brain tissue were detected by immunohistochemistry. The expressions of vascular endothelial growth factor (VEGF), Notch1, and intracellular domain of Notch (NICD) in ischemic cortex of brain tissue were detected by Western blotting. Results: The score of neural dysfunction and cell damage rate in model group were significantly increased (P < 0.01); The score of nerve function defect and rate of cell damage in each administration group were significantly reduced (P < 0.05, 0.01), the effect of borneol + AST IV + PNS group was better than that of single drug and AST IV + PNS group (P < 0.05, 0.01). NeuN and EBA protein expressions were significantly decreased in the ischemic cortex of model group (P < 0.01), while NeuN and EBA protein expressions were significantly enhanced in each administration group (P < 0.05, 0.01), and the effect of borneol + AST IV + PNS group was better than that of single drug and AST IV + PNS group (P < 0.05, 0.01). In model group, VEGF protein expression was increased significantly (P < 0.05), while NICD and Notch1 protein expression had no significant change. The expression of VEGF, NICD and Notch1 protein were significantly up-regulated in borneol + AST IV + PNS group (P < 0.01), and the effect of combination of three drugs was better than that of single drug and AST IV + PNS (P < 0.05, 0.01). Conclusion: Borneol, AST IV, and PNS have the effects of preventing neuronal and cerebral microvascular damage after CIRI, and the effect of combination of three drugs was better than that of single drug and AST IV + PNS, which may be related to the activation of the Notch signaling pathway and up-regulation of VEGF expression, thereby, exerting protective effects on ischemic brain tissue.

Study on transdermal permeation of ethanol extracts from roots of Gentiana crassicaulis in vitro and in vivo / 中草药

Objective: To establish a determination method for kinds of chemical components of iridoids in the roots of Gentiana crassicaulis in transdermal absorption liquid, and research its transdermal permeability, so as to provide scientific basis for transdermal delivery system, clinical medication and reform of the traditional forms of G. crassicaulis. Methods: Based on the results of the previous investigation, in this paper, using the roots of G. crassicaulis as the research subject, a certain concentration solution of G. crassicaulis extract was prepared by the alcohol extraction method. Three kinds of common penetration enhancers, azone, borneol and propylene glycol were used. The effects of single penetration enhancer and dual compound penetration enhancers on the transdermal penetration of five kinds of chemical components of loganic acid, shanzhiside methyl ester, swertimarin, gentiopicroside and sweroside in vitro and the three kinds of chemical components of gentiopicroside, loganic acid and swertimarin in vivo were quantitatively studied by the method of HPLC to investigate the transdermal permeability of G. crassicaulis extract in mice skin model. Results: According to the experimental results, compared to the control group, penetration enhancers significantly increased the absorption of five chemical components of G. crassicaulis in vitro. Transdermal absorption rates (J) of loganic acid, shanzhiside methyl ester, swertimarin, gentiopicroside and sweroside were 12.306 0, 1.248 8, 4.187 5, 153.030 0 and 5.012 6 μg/(cm2∙h), respectively. The transdermal enhancer effects of A (5% azone), B (5% borneol), C (5% propylene glycol), A + B (2.5% azone and 2.5% borneol), A + C (2.5% azone and 2.5% propylene glycol), A + C (2.5% borneol and 2.5% propylene glycol) were 9.73, 2.57, 13.94, 15.92 and 8.08 times faster than the control group, respectively. Among these, the group of A + C had a marked osmotic enhancer effect in vitro. In comparison with the control group, the in vivo percutaneous penetration test indicated that the dual compound penetration enhancers of 2.5% azone and 2.5% propylene glycol had a marked effect for the permeability enhancement. Conclusion: This study showed azone and propylene glycol significantly promoted the percutaneous penetration effect of loganic acid, shanzhiside methyl ester, swertimarin, gentiopicroside and sweroside of G. crassicaulis, and this study laid a foundation for the quality control of percutaneous drug delivery preparation of G. crassicaulis.

Effects of natural borneol and synthetic borneol on the transdermal absorption of emodin / 中国药学杂志

OBJECTIVE: To investigate the effect of natural and synthetic borneol on the transdermal absorption of emodin. METHODS: The supplying and receiving solutions containing emodin were selected from the abdominal skin of mice in vitro, and the samples were analyzed by HPLC. The cumulative permeability, permeability rate and permeability enhancement factor were used as the evaluation indexes of the permeability enhancement effect. RESULTS: The saline containing 1% Tween 80-80% ethanol and 60% ethanol could increase the solubility of emodin to 648 μg•mL -1 and obtain conditions of leaking trough. The penetration rate of emodin was 648 μg•mL - 1 > 569 μg•mL -1 > 457 μg•mL -1 in the range of concentration. The penetration enhancement effect of synthetic borneol was 2% > 4% > 1% > blank control group > 3% and 5%, and the steady-state permeation rates of 2% natural borneol (15.90 μg•cm- 2•h - 1 ) were higher than those of 2% synthetic borneol(12.44 μg•cm-2•h-1). CONCLUSION: Natural borneol and synthetic borneol can promote the transdermal penetration of emodin, which is limited by their concentration. This provides an experimental basis for the selection of emodin transdermal enhancers.