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Current Bioactive Compounds

Author(s): Vishal Gokul Beldar*, Manojkumar Jadhao and Kirti Laddha

DOI: 10.2174/1573407218666220304101139

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Development of a Simple, Rapid, and Economical Method for Extraction and Isolation of 3-O-acetyl-11-keto-β-boswellic Acid from the Resins of Boswellia serrata

Article ID: e040322201700 Pages: 7

  • * (Excluding Mailing and Handling)

Abstract

Background: Boswellia serrata is an important species from the Boswellia genus, which contains a variety of significant phytoconstituents. Numerous applications of the B. Serrata have been mentioned in the literature of the Indian ayurvedic system. Researchers reported abundant pharmacological activities of B. Serrata resins extract. The extract produces synergistic pharmacological activity due to the presence of the Boswellia acids and their derivatives. Among all Boswellia acids, 3-O-acetyl-11-keto-β-boswellic acid (AKBA) was found to be more potent. Traditionally, column chromatography was used for the isolation of AKBA from raw material as well as extracts. However, the column chromatography method was monotonous and timeconsuming.

Objective: The main goal of the research was to develop a new, simple, rapid, and reproducible method for the isolation of AKBA from the resin extract of B. Serrata.

Methods: The extraction and isolation of AKBA involved extraction of resins using hydroalcoholic solution followed by alkali treatment. The alkali solution was further treated with acid to precipitate the crude AKBA.

Results: The obtained crude AKBA was subjected to the dry column vacuum chromatography to separate and yield the high purity of the AKBA. The purity of the isolated AKBA was established by TLC & UHPLC. Spectral characterization of the isolated compound was performed by employing IR, MS, and NMR.

Conclusion: The proposed method can be used to isolate AKBA from resin extract of B. Serrata. Some modifications in this method lead to the large-scale production of highly pure AKBA for various pharmaceutical applications.

Keywords: Boswellia serrata, Pentacyclic triterpenoids, Boswellic acids, AKBA, Extraction and Isolation, DCVC.

Graphical Abstract

[1]
Marefati, N.; Beheshti, F.; Memarpour, S.; Bayat, R.; Naser Shafei, M.; Sadeghnia, H.R.; Ghazavi, H.; Hosseini, M. The effects of acetyl-11-keto-β-boswellic acid on brain cytokines and memory impairment induced by lipopolysaccharide in rats. Cytokine, 2020, 131(January), 155107.
[http://dx.doi.org/10.1016/j.cyto.2020.155107]
[2]
Al-Dhubiab, B.E.; Patel, S.S.; Morsy, M.A.; Duvva, H.; Nair, A.B.; Deb, P.K.; Shah, J. The beneficial effect of boswellic acid on bone metabolism and possible mechanisms of action in experimental osteoporosis. Nutrients, 2020, 12(10), 1-14.
[http://dx.doi.org/10.3390/nu12103186]
[3]
Sharma, T.; Jana, S. Boswellic acids as natural anticancer medicine: Precious gift to humankind. J. Herb. Med., 2020, 20, 100313.
[http://dx.doi.org/10.1016/j.hermed.2019.100313]
[4]
Iram, F.; Khan, S.A.; Husain, A. Phytochemistry and potential therapeutic actions of boswellic acids: A mini-review. Asian Pac. J. Trop. Biomed., 2017, 7(6), 513-523.
[http://dx.doi.org/10.1016/j.apjtb.2017.05.001]
[5]
Jin, L.; Yingchun, W.; Zhujun, S.; Yinan, W.; Dongchen, W.; Hui, Y.; Xi, Y.; Wanzhou, Z.; Buluan, Z.; Jinhua, W. 3-acetyl-11-keto-beta-boswellic acid decreases the malignancy of taxol resistant human ovarian cancer by inhibiting multidrug resistance (MDR) proteins func-tion. Biomed. Pharmacother., 2019, 116(May), 1-7.
[http://dx.doi.org/10.1016/j.biopha.2019.108992]
[6]
Katragunta, K.; Siva, B.; Kondepudi, N.; Vadaparthi, P.R.R.; Rama, N.; Kumar, A.; Suresh, K. Estimation of boswellic acids in herbal for-mulations containing boswellia serrata extract and comprehensive characterization of secondary metabolites using UPLC-Q-Tof-MSe. J. Pharm. Anal., 2019, 9, 414-422.
[http://dx.doi.org/10.1016/j.jpha.2019.09.007]
[7]
Hussain, H.; Al-harrasi, A.; Csuk, R.; Shamraiz, U.; Ivan, R.; Ahmed, I.; Khan, I.A.; Ali, Z.; Hussain, H.; Al-harrasi, A. Expert opinion on therapeutic patents therapeutic potential of boswellic acids: A patent review (1990-2015). Expert Opin. Ther. Pat., 2017, 00(00), 1-10.
[http://dx.doi.org/10.1080/13543776.2017.1235156]
[8]
Al-Harrasi, A.; Al-Saidi, S. Phytochemical analysis of the essential oil from botanically certified oleogum resin of boswellia sacra (Omani Luban). Molecules, 2008, 13(9), 2181-2189.
[http://dx.doi.org/10.3390/molecules13092181]
[9]
Rajabian, A.; Sadeghnia, H.R.; Hosseini, A.; Mousavi, S.H.; Boroushaki, M.T. 3-acetyl-11-keto-β-boswellic acid attenuated oxidative glu-tamate toxicity in neuron-like cell lines by apoptosis inhibition. J. Cell. Biochem., 2020, 121(2), 1778-1789.
[http://dx.doi.org/10.1002/jcb.29413]
[10]
Meka, B.; Ravada, S.R.; Murali Krishna Kumar, M.; Purna Nagasree, K.; Golakoti, T. Synthesis of new analogs of AKBA and evaluation of their anti-inflammatory activities. Bioorg. Med. Chem., 2017, 25(4), 1374-1388.
[http://dx.doi.org/10.1016/j.bmc.2016.12.045]
[11]
Mehta, M.; Satija, S.; Garg, M. Comparison between HPLC and HPTLC densitometry for the determination of 11-Keto- β -boswellic acid and 3- Acetyl-11-Keto- β -boswellic acid from boswellia serrata extract. Indian J. Pharm. Educ. Res., 2016, 50(3), 418-423.
[http://dx.doi.org/10.5530/ijper.50.3.15]
[12]
Ammon, H.P.T. Boswellic acids in chronic inflammatory diseases. Planta Med., 2006, 72(12), 1100-1116.
[http://dx.doi.org/10.1055/s-2006-947227]
[13]
Li, W.; Ren, L.; Zheng, X.; Liu, J.; Wang, J.; Ji, T.; Du, G. 3-O-acetyl-11-keto-β-boswellic acid ameliorated aberrant metabolic landscape and inhibited autophagy in glioblastoma. Acta Pharm. Sin. B, 2020, 10(2), 301-312.
[http://dx.doi.org/10.1016/j.apsb.2019.12.012]
[14]
Abdel-Tawab, M.; Werz, O.; Schubert-Zsilavecz, M. Boswellia serrata: An overall assessment of in vitro, preclinical, pharmacokinetic and clinical data. Clin. Pharmacokinet., 2011, 50(6), 349-369.
[http://dx.doi.org/10.2165/11586800-000000000-00000]
[15]
Wei, C.; Fan, J.; Sun, X.; Yao, J.; Guo, Y.; Zhou, B.; Shang, Y. Acetyl-11-keto-β-boswellic acid ameliorates cognitive deficits and reduces amyloid-β levels in APPswe/PS1dE9 mice through antioxidant and anti-inflammatory pathways. Free Radic. Biol. Med., 2019, 2020(150), 96-108.
[http://dx.doi.org/10.1016/j.freeradbiomed.2020.02.022]
[16]
Lv, M.; Shao, S.; Zhang, Q.; Zhuang, X.; Qiao, T. Acetyl-11-keto-β-boswellic acid exerts the anti-cancer effects via cell cycle arrest, apop-tosis induction and autophagy suppression in non-small cell lung cancer cells. OncoTargets Ther., 2020, 13, 733-744.
[http://dx.doi.org/10.2147/OTT.S236346]
[17]
Sharma, T.; Jana, S. A Validated lc-ms/ms method for simultaneous determination of 3-o-acetyl-11-keto-β-boswellic acid (AKBA) and its active metabolite acetyl-11-hydroxy-β-boswellic acid (Ac-11-OH-BA) in rat plasma: Application to a pharmacokinetic study. J. Chromatogr. Sci., 2020, 1-9.
[http://dx.doi.org/10.1093/chromsci/bmaa010]
[18]
Ahmed, M.A.E.; Ahmed, A.A.E.; El Morsy, E.M. Acetyl-11-keto-β-boswellic acid prevents testicular torsion/detorsion injury in rats by modulating 5-LOX/LTB4 and P38-MAPK/JNK/Bax/caspase-3 pathways. Life Sci., 2020, 260, 118472.
[http://dx.doi.org/10.1016/j.lfs.2020.118472]
[19]
Ahmad, S.; Khan, S.A.; Kindelin, A.; Mohseni, T.; Bhatia, K.; Hoda, M.N.; Ducruet, A.F. Acetyl-11-keto-β-boswellic acid (AKBA) attenu-ates oxidative stress, inflammation, complement activation and cell death in brain endothelial cells following OGD/reperfusion. Neuromolecular Med., 2019, 21(4), 505-516.
[http://dx.doi.org/10.1007/s12017-019-08569-z]
[20]
Anthoni, C.; Laukoetter, M.G.; Rijcken, E.; Vowinkel, T.; Mennigen, R.; Müller, S.; Senninger, N.; Russell, J.; Jauch, J.; Bergmann, J. Mechanisms underlying the anti-inflammatory actions of boswellic acid derivatives in experimental colitis. Am. J. Physiol. Gastrointest. Liver Physiol., 2006, 290(6), 1131-1137.
[http://dx.doi.org/10.1152/ajpgi.00562.2005]
[21]
Shamraiz, U.; Hussain, H.; Ur Rehman, N.; Al-Shidhani, S.; Saeed, A.; Khan, H.Y.; Khan, A.; Fischer, L.; Csuk, R.; Badshah, A. Synthesis of new boswellic acid derivatives as potential antiproliferative agents. Nat. Prod. Res., 2020, 34(13), 1845-1852.
[http://dx.doi.org/10.1080/14786419.2018.1564295]
[22]
Niphadkar, S.; Rathod, V. Optimization of microwave-assisted extraction of acetyl 11 keto β boswellic acid (AKBA) from boswellia serra-ta by using orthogonal array design (OAD). J. Biol. Act. Prod. from Nat., 2018, 8(2), 90-103.
[http://dx.doi.org/10.1080/22311866.2018.1461578]
[23]
Greve, H.L.; Kaiser, M.; Brun, R.; Schmidt, T.J. Terpenoids from the oleo-gum-resin of boswellia serrata and their antiplasmodial effects in vitro. Planta Med., 2017, 83, 1214-1226.
[http://dx.doi.org/10.1055/s-0043-116943]
[24]
Jiang, X.; Wang, Y.; Zhang, B.; Fei, X.; Guo, X.; Jia, Y.; Yu, W. Acetyl-11-keto-β-boswellic acid regulates the repair of rat sciatic nerve injury by promoting the proliferation of schwann cells. Life Sci., 2020, 254, 116887.
[http://dx.doi.org/10.1016/j.lfs.2019.116887]
[25]
Lv, M.; Zhuang, X.; Zhang, Q.; Cheng, Y.; Wu, D.; Wang, X.; Qiao, T. Acetyl-11-keto-β-boswellic acid enhances the cisplatin sensitivity of non-small cell lung cancer cells through cell cycle arrest, apoptosis induction, and autophagy suppression via P21-dependent signaling pathway. Cell Biol. Toxicol., 2020, 37, 209-228.
[http://dx.doi.org/10.1007/s10565-020-09541-5]
[26]
Badria, F.; Mazyed, E. Formulation of nanospanlastics as a promising approach for improving the topical delivery of a natural leukotriene inhibitor (3-acetyl-11-keto-β-boswellic acid): Statistical optimization, in vitro characterization, and ex vivo permeation study. Drug Des. Devel. Ther., 2020, 14, 3697-3721.
[http://dx.doi.org/10.2147/DDDT.S265167]
[27]
Liu, M.; Liu, T.; Shang, P.; Zhang, Y.; Liu, L.; Liu, T.; Sun, S. Acetyl-11-keto-β-boswellic acid ameliorates renal interstitial fibrosis via klotho/TGF-β/smad signalling pathway. J. Cell. Mol. Med., 2018, 22(10), 4997-5007.
[http://dx.doi.org/10.1111/jcmm.13766]
[28]
Sun, M-X.; He, X-P.; Huang, P-Y.; Qi, Q.; Sun, W-H.; Liu, G-S.; Hua, J. Acetyl-11-keto-β-boswellic acid inhibits proliferation and induces apoptosis of gastric cancer cells through the phosphatase and tensin homolog/Akt/cyclooxygenase-2 signaling pathway. World J. Gastroenterol., 2020, 26(38), 5822-5835.
[http://dx.doi.org/10.3748/wjg.v26.i38.5822]
[29]
Wang, S.; Wang, H.; Sun, B.; Li, D.; Wu, J.; Li, J.; Tian, X.; Qin, C.; Chang, H.; Liu, Y. Acetyl-11-keto-β-boswellic acid triggers premature senescence via induction of DNA damage accompanied by impairment of dna repair genes in hepatocellular carcinoma cells in vitro and in vivo. Fundam. Clin. Pharmacol., 2020, 34(1), 65-76.
[http://dx.doi.org/10.1111/fcp.12488]
[30]
Al-Bahlani, S.; Burney, I.A.; Al-Dhahli, B.; Al-Kharusi, S.; Al-Kharousi, F.; Al-Kalbani, A.; Ahmed, I. Boswellic acid sensitizes gastric cancer cells to cisplatin-induced apoptosis via P53-mediated pathway. BMC Pharmacol. Toxicol., 2020, 21(64), 1-10.
[http://dx.doi.org/10.1186/s40360-020-00442-1]
[31]
Liu, Y. Acetyl-11-keto-β-boswellic acid suppresses docetaxel-resistant prostate cancer cells in vitro and in vivo by blocking akt and stat3 signaling, thus suppressing chemoresistant stem cell-like properties. Acta Pharmacol. Sin., 2019, 40(5), 689-698.
[http://dx.doi.org/10.1038/s41401-018-0157-9]
[32]
Sailer, E.R.; Subramanian, L.R.; Rall, B.; Hoernlein, R.F.; Ammon, H.P.T.; Safayhi, H. Acetyl-11-Keto-β-Boswellic Acid (AKBA): Struc-ture requirements for binding and 5-lipoxygenase inhibitory activity. Br. J. Pharmacol., 1996, 117(4), 615-618.
[http://dx.doi.org/10.1111/j.1476-5381.1996.tb15235.x]
[33]
Fan, P.; Li, T.; Ye, Y.; Luo, Q.; Yuan, H.; Lou, H. Synthesis and cytotoxic activity of boswellic acid analogues. Phytochem. Lett., 2016, 18, 99-104.
[http://dx.doi.org/10.1016/j.phytol.2016.09.009]
[34]
Khan, M.A.; Ali, R.; Parveen, R.; Najmi, A.K.; Ahmad, S. Pharmacological evidences for cytotoxic and antitumor properties of boswellic acids from boswellia serrata. J. Ethnopharmacol., 2016, 191, 315-323.
[http://dx.doi.org/10.1016/j.jep.2016.06.053]
[35]
Sharma, N.; Bhardwaj, V.; Singh, S.; Ali, S.A.; Gupta, D.K.; Paul, S.; Satti, N.K.; Chandra, S.; Verma, M.K. Simultaneous quantification of triterpenoic acids by high performance liquid chromatography method in the extracts of gum resin of boswellia serrata obtained by differ-ent extraction techniques. Chem. Cent. J., 2016, 1-10.
[http://dx.doi.org/10.1186/s13065-016-0194-8]
[36]
Niphadkar, S.S.; Rathod, V.K. Extraction of Acetyl 11-Keto- β -Boswellic Acids (AKBA) from boswellia serrata using ultrasound. Sep. Sci. Technol., 2017, 00(00), 1-9.
[http://dx.doi.org/10.1080/01496395.2016.1274326]
[37]
Niphadkar, S.S.; Bokhale, N.B.; Rathod, V.K. Extraction of Acetyl 11-Keto- β -Boswellic Acid (AKBA) from boswellia serrata plant oleo gum resin using novel three phase partitioning (TPP) technique. J. Appl. Res. Med. Aromat. Plants, 2017, 0–1(April)
[http://dx.doi.org/10.1016/j.jarmap.2017.04.007]
[38]
Yu, J.; Zhao, H.; Wang, D.; Song, X.; Zhao, L.; Wang, X. Extraction and purification of five terpenoids from olibanum by ultrahigh pres-sure technique and high-speed counter-current chromatography. J. Sep. Sci., 2017, 1-24.
[http://dx.doi.org/10.1002/jssc.201700215]
[39]
Pedersen, D.S.; Rosenbohm, C. Dry column vacuum chromatography. Synthesis (Stuttg), 2001, (16), 2431-2434.
[http://dx.doi.org/10.1055/s-2001-18722]