Pharmacodynamic and Pharmacokinetic Evaluation of Soy Lecithin Based Tablet of Boswellic Acid

Background: The oleo-gum resin of Boswellia serrata contains pentacyclic triterpenic acids known as Boswellic acids (BAs) that are responsible for the anti-inflammatory and anti-arthritic activities by inhibition of 5-lipoxygenase. Methods: Soylecithin based tablet formulation of an enriched extract of BAs were formulated and evaluated comparatively with the unformulated extract for bioavailability on rabbits and therapeutic efficacy against arthritis on rats targeting two primary constituent 11-keto ?-boswellic acid (KBA) and 3-O-acetyl 11-keto ?-boswellic acid (AKBA). Total BAs content in the enriched fraction was measured and characterized by HPLC analysis. Soy lecithin based tablet of BAs enriched extract was prepared and evaluated for different parameters. Tablets at 160 and 320 mg/kg, and unformulated extract 160 mg/kg was assessed on CFA-induced arthritic rat model and bioavailability was evaluated on the rabbit. Results: Tablet formulation showed two times higher efficacy in increasing hot plate reaction time, reduction in paw volume, and TNF-? levels compared to unformulated extract signifying enhanced systemic absorption and availability of the BAs at the site of action. The tablet at 320 mg/kg dose showed repair of articular surfaces with small areas of erosion and irregularities in the connective tissue. Plasma samples of rabbit showed identified peaks only for KBA. Conclusion: The soy lecithin based tablet of BAs enriched extract at both doses showed higher peak plasma concentration and AUC compared to unformulated enriched extract. The results of the study substantiated higher efficacy and bioavailability of B. serrata gum resin enriched extract in the form of lecithin based tablet formulation.

Improvement Effects of β-boswellic Acid on Hippocampal Neurons Cells Injury Induced by Oxygen-glucose Deprivation / 中国药房

OBJECTIVE：To study the imp rovement effects of β-boswellic acid on hippocampal neurons cells injury of rats induced by oxygen-glucose deprivation. METHODS ：The hippocampal neurons cell of rats were divided into normal control group ， model group and β-boswellic acid low-concentration ，medium-concentration and high-concentration groups （1，10，100 μmol/L）. Except for normal control group ，other groups were cultured with relevant medium and given oxygen glucose deprivation to induce oxygen-glucose deprivation induced injury model. MTT assay was adopted to detect cell viability. Chemical colorimetry was used to detect LDH activity in cell culture supernatant. Hoechst-PI staining was used to detect the morphology change of cells. Flow cytometry was used to detect early apoptosis rate of cells. The expression of apoptosis-related protein （Bcl-2，Bax and cleaved caspase-3） were detected by Western blot. RESULTS ：Compared with model group ，the survival rate of cells and protein expression of Bcl- 2 were increased significantly in β-boswellic acid medium-concentration and high-concentration groups （P＜ 0.01），while LDH activity ，early apoptosis rate ，protein expression of cleaved caspase- 3 and Bax were all decreased significantly （P＜0.05 or P＜0.01）. The densely stained nuclei and fragmentation decreased significantly. CONCLUSIONS ：β-boswellic acid can relieve oxygen-glucose deprivation induced injury of hippocampal neurons cells ，the mechanism of which may be associated with down-regulating the protein expression of cleaved caspase- 3 and Bax and up-regulating the protein expression of Bcl- 2.

3--Acetyl-11-keto- -boswellic acid ameliorated aberrant metabolic landscape and inhibited autophagy in glioblastoma

Glioblastoma is the most common and aggressive primary tumor in the central nervous system, accounting for 12%-15% of all brain tumors. 3--Acetyl-11-keto--boswellic acid (AKBA), one of the most active ingredients of gum resin from Birdw., was reported to inhibit the growth of glioblastoma cells and subcutaneous glioblastoma. However, whether AKBA has antitumor effects on orthotopic glioblastoma and the underlying mechanisms are still unclear. An orthotopic mouse model was used to evaluate the anti-glioblastoma effects of AKBA. The effects of AKBA on tumor growth were evaluated using MRI. The effects on the alteration of metabolic landscape were detected by MALDI-MSI. The underlying mechanisms of autophagy reducing by AKBA treatment were determined by immunoblotting and immunofluorescence, respectively. Transmission electron microscope was used to check morphology of cells treated by AKBA. Our results showed that AKBA (100 mg/kg) significantly inhibited the growth of orthotopic U87-MG gliomas. Results from MALDI-MSI showed that AKBA improved the metabolic profile of mice with glioblastoma, while immunoblot assays revealed that AKBA suppressed the expression of ATG5, p62, LC3B, p-ERK/ERK, and P53, and increased the ratio of p-mTOR/mTOR. Taken together, these results suggested that the antitumor effects of AKBA were related to the normalization of aberrant metabolism in the glioblastoma and the inhibition of autophagy. AKBA could be a promising chemotherapy drug for glioblastoma.

Optimization of extraction and purification process of effective components of Olibanum based on response surface method / 中草药

Objective: To optimize the extraction and purification process of the boswellic acids components in the frankincense. Methods: The extraction amount and extract yield of 13 boswellic acids (3-oxotirucall-8,24-dien-21-oic acid, 3α-acetoxy-tirucall-7, 24-dien-21-oic acid, 3-hydroxytirucall-8,24-dien-21-oic acid, acetyl 11α-methoxy-β-boswellic acid, 3α-hydroxy tirucall-7,24-dien- 21-oic acid, 11-keto-boswellic acid, 3-O-acetyl-α-boswellic acid, 3α-acetyloxylanosta-8,24-dien-21-oic acid, 3β-acetoxy-5α-lanosta- 8,24-dien-21-oic acid, 3-acetyl-11-keto-β-boswellic acid, 3-acetyloxy-tirucall-8,24-dien-21-oic acid, α-boswellic acid, β-boswellic acid) in frankincense were detected by UPLC-TQ/MS, the extraction method was investigated by single factor and response surface, the extraction solvent, ratio of solid to liquid, extraction time and extraction times were investigated on the extraction process, and the extract was purified by alkali dissolving acid precipitation method and the purification process parameters were investigated by single factor and orthogonal test to determine the best purification process. Results: The optimum condition for the extraction of the frankincense is that twenty times of 95% ethanol for four times reflux extraction and 62 min for each time. Optimum purification process was as following: Dissolve in lye pH 12-13, and the solution was precipitated at 0-4 ℃ with pH < 2 for 30 min. The purity of boswellic acids was 73.87%. Conclusion: The optimized extraction and purification process is stable and feasible, which is suitable for the extraction and purification of effective fraction of frankincense and beneficial to give full play to the medicinal value of frankincense and provide scientific basis for material basis research of frankincense.

Study on Improvement Effects of Z-guggulsterone Combined with Acetyl- 11-keto-β-boswellic Acid on Cerebral Ischemia- reperfusion Injury Model Rats / 中国药房

OBJECTIVE： To study the improvement effects of Z-guggulsterone （Z-GL） combined with acetyl-11-keto-β- boswellic acid （AKBA） on cerebral ischemia-reperfusion injury model rats. METHODS： Male SD rats were randomly divided into sham operation group， model group， Z-GL+AKBA low-dose and high-dose groups （25， 50 mg/kg）， with 10 rats in each group. Except for sham operation group， middle cerebral artery occlusion/reperfusion injury model was induced by suture method in other groups. Administration groups were given relevant medicine intragastrically after reperfusion； sham operation group and model groups were given constant volume of DMSO intragastrically， every 12 h， for consecutive 7 d. The neurological deficits were evaluated with modified Longa score； HE staining was performed to observe the pathological changes of cerebral tissue in rats； the area of cerebral infarction was measured by TTC， and the percentage of cerebral infarction area； TUNEL staining was performed to detect apoptotic neurons. The expression of CD34， VEGF and DLL4 were detected by immunofluoresence and immunoblotting assay， respectively. RESULTS： Compared with sham operation group， the number of cortical cells in the model group decreased and arranged irregularly， with obvious infarct area and obvious decrease of neovascularization； the neurological deficit score， the percentage of cerebral infarction area and TUNEL positive cells increased significantly， while the expression of CD34， VEGF and DLL4 decreased significantly （P＜0.05 or P＜0.01）. Compared with model group， the above symptoms of the rats in each administration group were significantly improved， the neurological deficit score， the percentage of cerebral infarction area and the number of TUNEL positive cells were significantly reduced； the expression levels of CD34， VEGF and DLL4 were significantly increased； the neurological deficit score， the percentage of cerebral infarction area and the number of TUNEL positive cells in Z-GL+AKBA high-dose group were significantly lower or less than low dose group； the expression of CD34 and DLL4 in high-dose group was significantly higher than low-dose group （P＜0.05 or P＜0.01）. CONCLUSIONS： Z-GL combined with AKBA can relieve neurological deficit and cerebral injury of cerebral ischemia-reperfusion injury model rats， which may be related to promoting angiogenesis and up-regulating the expression of VEGF and DLL4 protein， with a certain dose-dependent effect.

Study on Substitute Reference Substance Method with DRS Origin Software: A Case Study of Determination of 11-keto-β-boswellic Acid and 11-keto-β-acetyl-boswellic Acid in Frankincense by UHPLC / 中国药学杂志

OBJECTIVE： To establish a UHPLC method for determination of the contents of 11-keto-β-boswellic acid(KAB) and 11-keto-β-acetyl-boswellic acid(AKBA)in Frankincense and explore the suitability and accuracy of substitute reference substance method with DRS origin software for qualitative and quantitative determination of chromatographic peaks. METHODS ：The samples were separated by UHPLC for determination of AKBA and KBA. AKBA was used as a reference to investigate the accuracy of KBA identification using DRS origin software on 19 different C18 columns. The RSDs of relative correction factors were calculated for different detection wavelengths and instruments.The relative correction factor method and the external standard method were selected for quantification and the differences were compared. RESULTS: The established method met the requirements of methodology and the average recovery was 100.21%(n=6) with RSD of 2.47%. The DRS origin software can be used to accurately determine the chromatographic peaks. The correct factor of AKBA vs. KBA was 0.936 and it was consistent under different conditions. There were no significant differences between the content calculated by the relative correction factor method and by the external standard method. CONCLUSION： This method is intelligent, feasible, reliable and economical, and can be used for the determination of frankincense content.

Multi-component Quantification Analysis and Overall Quality Evaluation of Dieda Pills / 中国药学杂志

OBJECTIVE: To establish an HPLC method for simultaneous determination of nine components, i.e., paeoniflorin, naringin, hesperidin, neohesperidin, paeonol, asperosaponin , glycyrrhizic acid, curcumin and acetyl-11-keto-beta-boswellic acid, and evaluate the overall quality of Dieda pills. METHODS: The analysis was performed on an Agilent 1260 Infinity LC System with a diode array detector. The chromatographic separation was performed on Agilent Poroshell 120 EC-C18 (4.6 mm×100 mm, 2.7 μm) column. The mobile phase was a mixture of acetonitrile (mobile phase A) and water containing 0.1% phosphoric acid aqueous solution (mobile phase B). The gradient elution program was as follows: 5%-18%A for 0-7 min, keeping 18%A for 7-15 min, 18%-35%A for 15-27 min, 35%-60%A for 27-32 min, 60%-95%A for 32-42 min, keeping 95%A for 42-45 min.The flow rate was set at 1.0 mL•min-1, the column temperature was maintained at 30 ℃ and the injection volume was 5 μL. The detection wavelength was set at 230 nm for paeoniflorin, 283 nm for naringin, hesperidin and neohesperidin, 274 nm for paeonol, 212 nm for asperosaponin , 251 nm for glycyrrhizic acid, 440 nm for curcumin and 251 nm for acetyl-11-keto-beta-boswellic acid, respectively. RESULTS: All the nine components achieved good separation.The linear ranges fell with in the range of 0.1-1.0 μg for paeoniflorin, naringin, neohesperidin andacetyl-11-keto-beta-boswellic acid, 0.2-2.0 μg for hesperidin and asperosaponin , 0.04-0.4 μg for paeonol, 0.02-0.2 μg for glycyrrhizic acid and 0.01-0.1 μg for curcumin,respectively(r2≥0.999 8). The average recoveries (n=6) were 96.95%-100.4% and the RSDs were 0.21%-0.81%. CONCLUSION: The developed method is simple, accurate, reliable, and can be used for the overall quality control and quality evaluation of Dieda pills.

Quantitative study of ten main components in Shuangshenlong Capsule by HPLC coupled with wavelength switching and gradient elution method / 中草药

Objective: To establish HPLC coupled with wavelength switching and gradient elution method (HPLC-DVD) for simultaneous determination of ten main components (calycosin-7-glucoside, ruscogenin, amygdalin, ginsenoside Rb1, ginsenoside Re, ferulic acid, crocin I, salvianolic acid B, acetyl-11-keto-β-boswellic acid, and tanshinone IIA) in Shuangshenlong Capsule (SSLC). Methods: The chromatographic separation was achieved on Hypersil ODS C18 (150 mm × 4.0 mm, 3 μm) column with methanol- water (8∶2) T (A)-0.1% phosphoric acid solution (B) as mobile phases for gradient elution, at the flow rate of 0.6 mL/min; The detection wavelength was set at 260 nm for α-calycosin-7-glucoside, 280 nm for ruscogenin, 210 nm for amygdalin, 203 nm for ginsenoside Rb1 and ginsenoside Re, 320 nm for ferulic acid, 440 nm for crocin I, 286 nm for salvianolic acid B, 250 nm for acetyl-11-keto-β-boswellic acid, and 270 nm for tanshinone IIA. The volume of sample injection was 10 μL. Results :The ten active components were well separated and showed good linearity between mass concentration and peak area, such as calycosin-7-glucoside 3.88—69.86 mg/L (r = 0.999 2), ruscogenin 22.1—397.8 mg/L (r = 0.999 1), amygdalin 37.43—673.5 mg/L (r = 0.999 4), ginsenoside Rb1 45.15—812.72 mg/L (r = 0.999 6), ginsenoside Re 4.55—81.95 mg/L (r = 0.999 5), ferulic acid 3.06—55.15 mg/L (r = 0.999 4), crocin I 1.93—34.76 mg/L (r = 0.999 5), salvianolic acid B 15.68—282.15 mg/L (r = 0.999 6), acetyl-11-keto-β-boswellic acid 11.31—203.58 mg/L (r = 0.999 1), and tanshinone IIA 1.89—34.16 mg/L (r = 0.999 6). The precision was good, and RSD was not more than 1.27%. The repeatability was good, and RSD was not more than 1.28%. The stability was good in 8 h, and RSD was not more than 0.96%. The average recoveries and corresponding RSD values were 99.61% (1.21%), 100.11% (0.76%), 101.52% (0.62%), 101.22% (1.03%), 100.83% (1.14%), 98.94% (0.53%), 101.04% (1.09%), 100.05% (1.25%), 99.81% (0.68%), and 101.94% (1.31%), respectively. The contents of nine batches of calycosin-7-glucoside, ruscogenin, amygdalin, ginsenoside Rb1, ginsenoside Re, ferulic acid, crocin I, salvianolic acid B, acetyl-11-keto-β-boswellic acid, and tanshinone IIA were 0.142—0.158, 0.747—0.764, 1.578—1.619, 2.163—2.185, 0.235—0.251, 0.557—0.580, 0.105—0.122, 0.311—0.328, 0.605—0.624, 0.062—0.079 mg/capsule, respectively. Conclusion: HPLC coupled with wavelength switching and gradient elution method has been established for simultaneous determination of ten components in SSLC. The method is simple, quick, accurate, and it can be used for content determination and quality control of SSLC.

Effects of Processed Temperature And Time on Color and Contents of Six Types of Boswellic Acids in Frankinense / 世界科学技术-中医药现代化

This paper focused on factors which affected on different color of northern and southern region vinegar-processed frankincense.Meanwhile,contents of six main boswellic acids were also determined to elaborate the influence of heat in chemical components.Vinegar-processed frankincense from northern and southern region was collected.And different temperature and time were used in the processing of frankincense to receive the vinegar-processed frankincense samples.The color difference meter was utilized combining with the PCA statistic analysis method.The Zorbax ExtendC18 chromatographic column (4.6 mm × 50 mm,1.8 μm) was used with acetonitrile-0.1％ phosphoric acid as the mobile phase and gradient elution.The velocity of flow was 1 mL· min-1.The detection wavelength was 210 nm and 250 nm.The column temperature was 30℃.The results showed that the color of northern region processed frankincense was yellow or pale brown.And the southern region processed frankincense was pale brown or dark brown.It showed the difference on processed degree.The L* value of the northern processed frankincense was 75.327 to 80.746 and the L* value of southern processed was 44.321 to 49.527.The a* value of the northern processed frankincense was 5.378 to 6.502 and the a* value of southern processed was 9.423 to 9.978.There was no significant difference on b*.There were certain differences on L* and a* among vinegar-processed frankincense with the same surface color.The color parameter results of self-made vinegar-processed frankincense indicated that along with changes of processing temperature and time,the color,L* and a* change.Even frankincense processed for 30 min with mild fire,it will not achieve the color parameter value of the southern region vinegar-processed frankincense.However,after 11 min processing with medium fire,the color can be achieved.The content determination results showed that four contents,including α-boswellic acid,β-boswellic acid,3-acetyl-α-boswellic acid and 3-acetyl-β-boswellic acid were increased.Contents of 11-carbonyl-3-boswellic acid and 3-acetyl-11-carbonyl-β-boswellic were decreased after being processed.The range of increasing or decreasing by medium fire was higher than mild fire.At the same temperature,as the increasing of processing time,the content has an increasing or decreasing tendency.It was concluded that temperature was the main factor influencing the color of vinegar-processed frankincense from northern and southern regions.Different processing degrees also make influence on the contents of chemical compounds.The color parameter value can be used to evaluate the color of processed frankincense.

Simultaneous determination of six boswellic acids in Xihuang Pill by HPLC-ELSD / 中草药

Objective: To establish an HPLC-ELSD method for simultaneous determination of six kinds of boswellic acids including 11-carbonyl-β-boswellic acid, acetyl-11-carbonyl-β-boswellic acid, α-boswellic acid, β-boswellic acid, 3-acetyl-α-boswellic acid, and 3-acetyl-β-boswellic acid in 10 batches of Xihuang Pill (XHP). Methods: The separation was achieved on a Waters Symmetry C18 column (250 mm×4.6 mm, 5 μm) with the mobile phase consisting of methanol-0.5% acetic acid to be gradient elution. Flow rate was 0.8 mL/min and column temperature was 30℃. The samples were tested on Evaporative Light-scattering Detector with drift tube temperature of 45℃, carrier gas of purity N2, and carrier gas flow rate of 1.5 L/min. Results: 11-Carbonyl-β-boswellic acid, acetyl-11-carbonyl-β-boswellic acid, α-boswellic acid, β-boswellic acid, 3-acetyl-α-boswellic acid, and 3-acetyl-β-boswellic acid had good linearity in the ranges of 0.10-3.00 μg (r=0.9995), 1.23-36.9 μg (r=0.9995), 0.16-4.8 μg (r=0.9997), 0.25-7.5 μg (r=0.9997), 0.21-6.3 μg (r=0.9995), and 0.30-9.0 μg (r=0.9996), respectively. The average recoveries of the six boswellic acids were 99.6% (3.70%), 99.1% (3.62%), 99.2% (1.66%), 98.2% (1.89%), 99.1% (3.42%), and 99.5% (2.32%), respectively. Conclusion: This method is simple, reliable, and with good effect for the separation, and can provide the reference for study on XHP material basis.

Preparation technology and physico-chemical characteristics of Olibanum ultramicro powders / 中草药

Objective: To optimize the technology and evaluate the influence of micronization on Olibanum physic-chemical characteristics and dissolution. Methods: The single factor test was employed to investigate the effect of the size and freezing time of common powder particle, the ratio of excipients, and grinding time on the yield of ultramicro powder; Additionally a comparative research between ultramicro powder and common powder was designed, including micromeritic properties (angle of repose, bulk density, tap density, and squeezing degree), effective components concentration [volatile oil, octyl acetate and 3-acetyl-11-keto-β-boswellic acid (AKBA)], and cumulative dissolution rate. Results: The optimal technology of ultramicro powder was as follows: the medicinal material was ground into fine powder, followed by 4 h freezing at -20℃ and 15 min superfine grinding with excipient and fine powder in ratio of 1:5; As the degree of smashing enhanced, the angle of repose of powders increased, bulk density and tap density decreased, and compressibility had a tendency of increase as flowability declined; The concentration of octyl acetate had an increased tendency and then decreased. While the concentration of octyl acetate in ultrafine powder prepared by optimal technology was the highest, the cumulative dissolution rate of AKBA in the ultramicro powder was higher than that in common powder. Conclusion: The application of optimal superfine pulverizing technique to Olibanum is feasible, and appropriate degree of micronization is helpful for the extraction and dissolution of effective components in Olibanum.

Study on fingerprint analysis of Xihuang Pills by HPLC-ELSD / 中草药

Objective: To establish the quality evaluation of fingerprints of Xihuang Pills by HPLC-ELSD. Methods: The chromatography conditions were defined as waters C18 column (250 mm × 4.6 mm, 5 μm); Mobile phase was methanol-0.5% acetic acid, gradient elution; temperature of column was set at 30℃. The ELSD conditions were as follows: the temperature of drift tube was 45℃, the gas speed was 1.5 L/min. Ten batches of Xihuang Pills samples were analyzed for similarity analysis (SA), hierarchical clustering analysis (HCA) and principle component analysis (PCA). Results: The chromatographic fingerprint was completed with 25 recognizable peaks, and the samples with great differences and the compounds with greater impact on the quality were obtained through HCA and PCA. Conclusion: HPLC fingerprint combining with pattern recognition could reflect the intrinsic quality to provide a scientific basis for the quality control of Xihuang Pills.

Qualitative and Quantitative Determination Methods for Vinegar Frankincense in Liuwei Jingkang Capsules / 中国药师

Objective:To establish a quality standard for vinegar frankincense in Liuwei Jingkang capsules. Methods: TLC was used for the identification of vinegar frankincense. HPLC was used for the content determination of acetyl-11-keto-β-boswellic acid (AKBA), which was the main active component in vinegar frankincense. A SHIMADZU Shim-pack VP-ODS(250 mm × 4. 6 mm,5μm) column was used. The mobile phase consisted of acetonitrile and water containing 0. 01 mol·L-1 hydrochloric acid (78 ∶22) at a flow rate of 1. 5 ml·min-1 . The column temperature was 30℃. The detection wavelength was 252 nm, and the injection volume was 10 μl. Results:The TLC method could identify the characteristic fluorescence of vinegar frankincense was without interference from the blank. There was a good linear relationship of AKBA within the concentration range of 0. 036 5-0. 730 8 mg·ml-1(r=0. 999 7). The average recovery was 98. 24% (RSD=0. 83%, n=9). Conclusion:The established method is accurate, highly sensitive and well re-producible, which can be used for the quality control of Liuwei Jingkang capsules.

A holistic strategy of identification and quality evaluation of frankincense by chromatographic fingerprint combined with chemometrics / 中国药学杂志

OBJECTIVE: To propose and establish a novel holistic strategy of identification and quality evaluation of frankincense by chromatographic fingerprint analysis. METHODS: The strategy contained five steps. The first step was multi-species sample collection. The second was to establish fingerprint identification and assay under the same chromatographic conditions. The third was components identification by means of reference substances and LC-MS. The fourth was multivariate analysis for identification and classification of certified products and adulterants. The fifth was to evaluate TCMs using similarity threshold and content range criteria. RESULTS: Twenty-six chromatographic peaks were separated and fourteen were identified. Furthermore, HCA heatmap analysis, principal component analysis, partial least squares discrimination, self-organizing map clustering, and support vector machine were used for pattern recognition. The common patterns for three species of frankincenses were established. The content ranges for KBA and AKBA were also calculated. CONCLUSION: The method is specific and can be used to accurately identify and systematically evaluate medicinal frankincense.

Protective Effect of Acetyl-11-keto-β-boswellic Acid on Myocardial Ischemia Induced by Isoproterenol Hydrochloride in Rats / 中国药师

Objective:To study the effects and mechanisms of acetyl-11-keto-β-boswellic acid ( AKBA) in myocardial ischemic model induced by isoproterenol hydrochloride ( ISO) in rats. Methods:The SD rats were randomly divided into the sham group, model group, AKBA low dose group and AKBA high dose group. Myocardial injury model was induced by subcutaneous injection of ISO (100 mg·kg-1 ) . The change of ST segment in ECG was observed. Creatine kinase ( CK-MB) , cardiac troponin I ( cTnI) , lactate dehydro-genase( LDH) , malondialdehyde( MDA) and superoxide dismutase( SOD) in the blood were detected by ELISA. The change of histo-logical tissue was determined by HE staining, and cell apoptosis was analyzed by TUNEL assay. Results: Serum CK-MB, cTnI and LDH were decreased significantly in AKBA high dose group when compared with those in the model group. Compared with that in the model group, MDA content was lowered and the SOD activity was increased in AKBA high dose group. Furthermore, AKBA high dose group improved the pathologic changes of myocardium. TUNEL assay revealed significant reduction of cardiomyocytes apoptosis in the hearts of the ischemic rats in AKBA high dose group. Conclusion:AKBA has excellent cardioprotective effect on myocardial ischemic induced by ISO and protection of myocardial cells from injury.

Simultaneous determination of six components in Bawei Chenxiang Powder by HPLC-DAD / 中草药

Objective: To develop an HPLC method for simultaneous determination of gallic acid, protocatechuic acid, costunolide, dehvdrocostuslactone, ehydrodiisoeugenol, and acetyl-11-keto-β-boswellic acid in Bawei Chenxiang Powder (BCP). Methods: The chromatographic separation was achieved on a Waters XBridge-C18 column (250 mm × 4.6 mm, 5.0 μm) with methanol-acetonitrile (50:50, A) and methanol-0.1% acetic acid (10:90, B) as mobile phases at the flow rate of 0.8 mL/min for gradient elution, and the column temperature was 35℃. Its linear relationship, precision, repeatability, stability, and recoveries were investigated. Results: The seven components were well separated and showed good linearity, such as gallic acid 1.5-30.0 mg/L (r = 0.999 0), protocatechuic acid 1.0-20.0 mg/L (r = 0.999 2), costunolide 2.0-40.0 mg/L (r = 0.999 1), dehvdrocostuslactone 2.0-40.0 mg/L (r = 0.999 3), ehydrodiisoeugenol 0.2-4.0 mg/L (r = 0.999 4), and acetyl-11-keto-β-boswellic acid 3.5-70.0 mg/L (r = 0.999 1). The precision was good, and RSD value was less than 2.0%. The repeatability was good, and RSD was less than 2.0%. The stability was good in 24 h. The average recoveries were between 98.49% and 101.55% (RSD ≤ 2.0%). Conclusion: The method is accurate, sensitive, credible, and repeatable. It can be applied to the quality control of BCP.

Absorption of 3-acetyl-11-keto-β-boswellic acid in Caco-2 cells and MDCK cell models / 中草药

Objective: To study the mechanisms of absorption and transport of 3-acetyl-11-keto-β-boswellic acid (AKBA) from Boswellia carterif in Caco-2 cell, MDCK-MDR1, and MDCK-Wild cell models. Methods: The Caco-2, MDCK-MDR1, and MDCK-Wild cell monolayer models were used to study the bi-directional transport of AKBA in apical (AP)→basal (BL) or BL→AP; The concentration of AKBA was measured by LC-MS/MS and apparent permeability coefficient (Papp) was calculated. Results: Papp (AP→BL) and Papp (BL→AP) values of AKBA (50 μmol/L) in Caco-2 cell model were 7.9 × 10-7 and 1.5 × 10-7 cm/s, respectively; Papp (AP→BL) and Papp (BL→AP) values of AKBA (50 μmol/L) in MDCK-MDR1 cell model were 2.6 × 10-7 and 0.8 × 10-7 cm/s, respectively; Papp (AP→BL) and Papp (BL→AP) of AKBA (50 μmol/L) in MDCK-Wild cell model was 2.4 × 10-7 and 0.6 × 10-7 cm/s, respectively; The rates of efflux (RE) for AKBA in Caco-2 and MDCK-MDR1 cell monolayers were both smaller than 2. Conclusion: AKBA is not the substrate of P-gp and its absorption rate is low. AKBA is absorbed through the intestinal epithelial cells by active transport absorption and passive diffusion possibly.

Analysis on in vivo metabolic pathways of 3-acetyl-11-keto-β-boswellic acid in rats / 中草药

Objective: To study the in vivo metabolic pathways of 3-acetyl-11-keto-β-boswellic acid (AKBA) in rats. Methods: An HPLC-QTRAP-MS method was applied to identifying the metabolites of AKBA in bile, urine, and feces after ig administration of AKBA 60 mg/kg to rats. Results: A total of 15 metabolites were found in rats. The major metabolic pathways of AKBA were deacetylation, mono-hydroxylation, dehydrogenation, and glucuronide conjugates. Conclusion: AKBA undergoes the extensive phases I and II metabolism in rats; The metabolites produced mainly excrete through feces and bile; The information-dependent acquisition (IDA) and enhanced product ion (EPI) scan were used on a linear ion trap mass spectrometer to get high quality MS2 picture and provide an effective method for identifying the metabolites of AKBA.

Efficacy of boswellic acid on lysosomal acid hydrolases, lipid peroxidation and anti-oxidant status in gouty arthritic mice

<p><b>OBJECTIVE</b>To evaluate the efficacy of boswellic acid against monosodium urate crystal-induced inflammation in mice.</p><p><b>METHODS</b>The mice were divided into four experimental groups. Group I served as control; mice in group II were injected with monosodium urate crystal; group III consisted of monosodium urate crystal-induced mice who were treated with boswellic acid (30 mg/kg/b.w.); group IV comprised monosodium urate crystal-induced mice who were treated with indomethacin (3 mg/kg/b.w.). Paw volume and levels/activities of lysosomal enzymes, lipid peroxidation, anti-oxidant status and inflammatory mediator TNF-α were determined in control and monosodium urate crystal-induced mice. In addition, the levels of β-glucuronidase and lactate dehydrogenase were also measured in monosodium urate crystal-incubated polymorphonuclear leucocytes (PMNL) in vitro.</p><p><b>RESULTS</b>The activities of lysosomal enzymes, lipid peroxidation, and tumour necrosis factor-α levels and paw volume were increased significantly in monosodium urate crystal-induced mice, whereas the activities of antioxidant status were in turn decreased. However, these changes were modulated to near normal levels upon boswellic acid administration. In vitro, boswellic acid reduced the level of β-glucuronidase and lactate dehydrogenase in monosodium urate crystal-incubated PMNL in concentration dependent manner when compared with control cells.</p><p><b>CONCLUSIONS</b>The results obtained in this study further strengthen the anti-inflammatory/antiarthritic effect of boswellic acid, which was already well established by several investigators.</p>

Research progress of acetyl-11-keto-β-boswellic acid on its anti-cancer activity / 肿瘤研究与临床

Acetyl-11-keto-β-boswellic acid (AKBA) is one of the triterpenes in the gum resin of the Boswellia serrata and Boswellia carterii,also known as Salai guggal or Indian frankincense.There has been growing interst in anti-tumor activity of AKBA.This review will summarize the latest advances of AKBA on anti-tumor activity for the better understanding of this compound and its further applications.