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.

Advances in preclinical studies on borneol as an adjuvant for glioma / 药学实践杂志

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 / 药学实践杂志

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.

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.

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.

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.

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 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.

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

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.

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.

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.

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.

Effects of borneol on the pharmacokinetics of vinpocetine in rats / 药学学报

Vinpocetine (VP) has been widely used to treat cerebrovascular disorders and nerve injury. Borneol (BN), as an important traditional Chinese medicine, is commonly used to promote the absorption and distribution of central nervous system drugs. In this work, a LC-MS/MS method was developed to determine the level of VP in rat plasma and tissues, and to evaluate the effect of co-administration of BN with VP by oral gavage on the absorption and tissue distribution of VP in rats. Rats were divided into VP (10 mg·kg-1), VP (10 mg·kg-1) + BN (75 mg·kg-1) and VP (10 mg·kg-1) + BN (150 mg·kg-1) groups for pharmacokinetic study, and divided into VP (10 mg·kg-1) and VP (10 mg·kg-1) + BN (150 mg·kg-1) groups for tissue distribution study. The animal experiment was approved by Ethics Committee of Hubei University, and complied with the guideline for caring and using of laboratory animals. Compared to VP group, the AUC0-∞, MRT0-∞ and t1/2z of VP + BN (150 mg·kg-1) group increased significantly, by 1.98-, 1.22- and 1.42-fold respectively, and the exposure in plasma, liver, kidney and brain increased by 2-, 1.5-, 1.5- and 1.3-fold respectively. The pharmacokinetic results suggested that co-administration of BN with VP is beneficial for overcoming the undesirable pharmacokinetic characteristics of VP, such as short residence time, low oral bioavailability and brain exposure in clinical usage.

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.

Synergic effect of Chuanxiong Rhizoma and borneol on protecting hippocampus and hypothalamus of rats from global cerebral ischemia reperfusion injury / 中国药理学通报

To research the synergic effect of Chuanxiong Rhizoma(CR) and borneol(BO) on pro-tecting hippocampus and hypothalamus of the rats from global cerebral ischemia reperfusion (GCIR) injury. Methods GCIR rats were divided into five groups, i. e. sham, model, CR(1.0 g kg"1), B0(0. 16 g kg"1) and CR + BO groups. The contents of Glu, Gly and GABA in brain microdialysis solution were detected by GC-MS. [Ca2+]i of the two regions were measured using a confocal microscope. The apoptotic rate and ultrastructure were obtained by TUNEL stain and transmission electron microscopy, respectively. Results The monotherapy of CR or BO attenuated Ca2 + over-load and improved ultrastructure in both areas. Their synergy showed a better effect. CR alone reduced the apoptotic rate, increased the levels of GABA in both brain areas, while BO only decreased that of Glu. The combination even enhanced the content of Gly in hypothalamus. Conclusions Obvious synergic effects between CR and BO exist in attenuating neuroceliular ex-citotoxicity and calcium overload, while the anti-apop-totic effect might be excluded.

Effect of borneol combined with astragaloside IV and Panax notoginseng saponins on permeability of blood-brain barrier after cerebral ischemia-reperfusion / 中国药理学通报

Aim To probe the effect of borneol combined with astragalosides IV (AST I V) and Panax notoginseng saponins (PNS) on blood-brain barrier (BBB) after cerebral ischemia-reperfusion. Methods Rats with cerebral ischemia-reperfusion were administered by gavage, the symptom of nerve function defect was observed, the water content of brain tissues, the permeability of BBB, and the expression of zonula cccludens 1 (ZO-1), ZO-2, Occludin and Claudin-5 were detected. Results After cerebral ischemia-reperfusion, the neurological deficit symptom appeared, the neurological function score and brain water content increased, and BBB was destroyed. Each drug could relieve the above pathological changes to various degrees, and the effect of borneol + AST IV + PNS was the best, which was stronger than that of single drug and AST IV + PNS. The expressions of ZO-1, ZO-2, Occludin, Claudin-5 proteins decreased after cerebral ischemia-reperfusion. All drugs inhibited the decrease of ZO-1, except AST I V, and increased Occludin expression; Borneol + AST IV + PNS also up-regulated ZO-2, and the increase in ZO-1, ZO-2, Occludin was greater than that of each drug alone and AST IV + PNS. Conclusions Borneol, AST IV and PNS can relieve the increase of BBB permeability, reduce brain edema and antagonize brain injury to various degrees after cerebral ischemia-reperfusion, which are enhanced by the combination of three drugs. The mechanism may be related to the synergistic inhibition of the down-regulation of ZO-1, ZO-2 and Occludin and the protection of BBB after cerebral ischemia.

Study on borneol combined with astragaloside IV and Panax notoginseng saponins promoting bioactive components into brain in cerebral ischemia/reperfusion model of rats / 中草药

Objective To investigate whether borneol can promote the bioactive components of the combination of astragaloside IV (AST IV) and Panax notoginseng saponins (PNS) into the blood-brain barrier of rats with middle cerebral artery occlusion (MCAO)/reperfusion. Methods Using the model of MCAO/reperfusion, rats were randomly divided into sham-operation group, model group, borneol group, AST IV group, PNS group, AST IV + PNS group and borneol + AST IV + PNS group, and the content of AST IV and the bioactive components of PNS (ginsenoside Rg1, ginsenoside Rb1, and notoginsenoside R1) in the cerebral cortex and the cerebellum of the affected side and the healthy side were determined by liquid chromatography-mass spectrometry (LC-MS/MS). Results AST IV, whether used alone or combined with PNS and borneol, was mainly distributed in the cerebral cortex after oral administration, especially in the affected cerebral cortex. Borneol combined with AST IV and PNS significantly increased the content of AST IV in the affected and the healthy cerebral cortex. The bioactive components of PNS such as ginsenoside Rg1, ginsenoside Rb1, and notoginsenoside R1 was mainly distributed in the affected side of the cerebellum when PNS was used alone. Borneol combined with AST IV + PNS significantly increased the content of ginsenoside Rb1 in the cerebral cortex, especially in the affected cortex, increased the content of Rg1 in the healthy and the affected cortex, and increased the content of notoginsenoside R1 in the cerebral cortex, especially in the affected cortex, as well as in the cerebellum. Conclusion AST IV and the bioactive components of PNS such as ginsenoside Rg1, ginsenoside Rb1, and notoginsenoside R1 have a certain distribution in the cerebral cortex and the cerebellum after cerebral ischemia-reperfusion in rats. AST IV was mainly distributed in the cerebral cortex when it was used alone, ginsenoside Rg1, ginsenoside Rb1, and notoginsenoside R1 were mainly distributed in the cerebellum when PNS was used alone. The combination of borneol combined with AST IV and PNS can promote the gather of AST IV, ginsenoside Rg1, ginsenoside Rb1, and notoginsenoside R1 to the cerebral cortex, especially to the cortex of the ischemia-reperfusion side; Moreover, it can promote the absorption of AST IV, ginsenoside Rg1, ginsenoside Rb1, and notoginsenoside R1 in the cerebral cortex to varying degrees, especially in the affected cortex.

Establishment and application of fingerprint and quantitative method of volatile components in Shuangyu Granules / 中草药

Objective To establish the GC fingerprint and components quantitative determination of Shuangyu Granules (SG) for quality control. Methods Agilent DB-1 capillary column (30 m × 0.32 mm, 0.25 μm) was used with upper column volume of 1 μL and split ratio of 25∶1; Injection port was 230 ℃ and detector temperatures was 250 ℃; The carrier gas was nitrogen and its flow rate was 0.6 mL/min. The column temperature was raised by program. Results The fingerprints with good separation and repeatability included 12 mutual common peaks, and the similarity of each batch was more than 0.95. Seven chemical components were identified by GC/MS and standard compounds, which were eucalyptol (peak 2), camphor (peak 3), menthone (peak 4), borneol (peak 5), menthol (peak 6), pulegone (peak 9), and undecanone (peak 10); Among which, peaks of 1, and 10—12 were from Houttuyniae Herba, peaks of 2 and 5 from Artemisiae Argyi Folium and Menthae Haplocalycis Herba, peak of 3 from Artemisiae Argyi Folium, peak of 4, 6, 8 and 9 from Menthae Haplocalycis Herba, peak of 7 from Menthae Haplocalycis Herba, Artemisiae Argyi Folium and Houttuyniae Herba. Moreover, eucalyptol and menthol were quantified and the average recovery rates of eucalyptol and menthol were 103.9% and 98.2% (RSD were 2.1% and 2.3%), respectively. The content of eucalyptol and menthol in 10 batches samples were 0.17—0.23 mg/g and 0.45—0.67 mg/g, respectively. Conclusion The method of fingerprint and quantitative analysis of two components in SG was rapid, simple, and accurate, which could be used for the quality control of SG.

Effect of borneol combined with astragaloside IV and Panax notoginseng saponins on transporter proteins of blood-brain barrier after cerebral ischemia-reperfusion / 中草药

Objective: To investigate the effects of borneol combined with astragaloside IV (AST IV) and Panax notoginseng saponins (PNS) on promoting the active components into the brain and anti-brain injury through the regulation of transporter proteins of blood-brain barrier (BBB) in the state of cerebral ischemia-reperfusion. Methods: Focal cerebral ischemia-reperfusion model in rats was established, borneol, AST IV, PNS and the combination were administered by gavage, brain infarction rate was evaluated by 2,3,5-triphenyl tetrazolium chloride (TTC) staining, the expressions of efflux proteins such as p-glycoprotein (P-gp), multidrug resistance protein (MRP)-1, MRP-2, MRP-4, MRP-5 and uptake proteins such as organic cation transporter (OCT)-3, organicanion transporting polypep-tides (OATP)-2 in brain tissues were detected by Western blotting. The expressions of multidrug resistance (MDR) such as mdr1a, mdr1b and mrp-1, mrp-2, mrp-4, mrp-5 mRNA in brain tissues were determined by real-time PCR method. Results: The results of TTC staining showed that brain infarct was found after cerebral ischemia-reperfusion. Each drug could significantly reduce brain infarction volume and decrease infarction rate, and the effect of AST IV + PNS was better than that of AST IV and PNS alone, the effect of borneol + AST IV + PNS was better than that of single drug and AST IV + PNS. The results of major efflux proteins and genes detection showed that the protein expressions of P-gp, MRP-1, MRP 2, MRP-4, and MRP-5 were significantly increased in rats after cerebral ischemia-reperfusion. Borneol could significantly down-regulate the expressions of P-gp, MRP-2, MRP-4 proteins, PNS could significantly down-regulate the levels of MRP-4, MRP-5 proteins; AST IV, AST IV + PNS and borneol + AST IV + PNS could significantly down-regulate P-gp, MRP-2, MRP-4, MRP-5 proteins, and the effects of borneol + AST IV + PNS were significantly better than those of single drug and AST IV + PNS; The effects of AST IV + PNS were significantly better than those of AST IV or PNS alone. The results of gene expressions were similar to those of protein expression. The results of major uptake proteins showed that the expression of OCT-3 protein did not change significantly in the model group and drug groups after cerebral ischemia-reperfusion; However, the expression of OATP-2 protein was significantly decreased in the model group. PNS, AST IV + PNS and borneol + AST IV + PNS could significantly up-regulate the expression of OATP-2 protein; Furthermore, the effect of borneol + AST IV + PNS was significantly greater than that of single drug and AST IV + PNS, and the effect of AST IV + PNS was significantly greater than that of AST IV and PNS alone. Conclusion: After cerebral ischemia-reperfusion, brain tissues were damaged, the expressions of major efflux proteins and genes on BBB were significantly increased, while the expression of uptake protein such as OATP-2 was significantly decreased. Borneol combined with AST IV and PNS can enhance the effect of anti-ischemic brain injury, which may be related to the down-regulations of the expressions of efflux proteins such as P-gp, MRP-2, MRP-4, MRP-5 and corresponding genes in BBB, as well as the up-regulation of the expression of uptake proteins such as OATP-2, thus promoting the absorption and the enrichment of borneol, AST IV and the effective components of PNS in brain tissues, playing a better role in pharmacology.