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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
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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.
