Research Highlights
2011 - 2012
on Boswellin from 2011 to 2012

Anti-arthritic activity of Glycyrrhiza glabra, Boswellia serrata and their synergistic activity in combined formulation studied in freund’s adjuvant induced arthritic rats
Mishra NK, Bstia S, Mishra G, Chowdary KA, Patra S
J Pharm Educ Res, 2011; 2(2).

The present study evaluated the anti-arthritic property of n-hexane extract of Boswellia serrata gum resin in male albino rats. Freund's adjuvant was used to induce the paw edema. Acid phosphatase (ACP) and paw edema volume were evaluated. Levels of ACP and paw edema volume were significantly decreased in Boswellia-treated group (P < 0.01) from day 0 to last day i.e., day 21. When compared to arthritic control, Boswellia-treated group was found significantly decreased in paw edema volume (P < 0.01). The study concluded that Boswellia serrata could be an effective adjuvant for arthritis management

Antistaphylococcal and biofilm inhibitory activities of acetyl-11-keto-b-boswellic acid from Boswellia serrata
Raja AF, Ali F, Khan IA, Shawl AS, Arora DS, Shah BA, Taneja SC
BMC Microbiology, 2011; 11:54

In this study, boswellic acids from gum resin of Boswellia serrata were subjected to microbial inhibition concentration (MIC) test. Acetyl–keto–β-boswellic acid (AKBBA) was found to be the most active, with the MIC range of 2-8µg/ml. It was further subjected to antibacterial assays on Staphylococcus aureus and Staphylococcus epidermidis. Post-antibiotic effect and time-kill kinetic studies of AKBBA-treated group was significant compared to the standard group treated with Ciprofloxacin (P < 0.05) and untreated group (P < 0.05), respectively. Biofilm inhibition and reduction and membrane integrity in AKBBA-treated group were significant compared to untreated group (P < 0.05). Similarly, membrane leakage was found to be significant in AKBBA-treated group compared to untreated group (P < 0.01). The study concludes that AKBBA could be a new anti gram-positive and anti-biofilm agent.

Evaluation of anti-ulcer activity of Boswellia serrata bark extracts using aspirin induced ulcer model in albino rats
Zeeyauddin K, Narsu ML, Abid M, Ibrahim M
J of Med and Al Sci, 2011; 1 (1): 14-20

The present study evaluated the anti-ulcer activity of petroleum ether (PBE) and aqueous (ABE) extracts of the bark of Boswellia serrata keeping ranitidine and rice bran oil as standard and control, respectively. Aspirin (200mg/kg) was given to all the groups to induce ulcers. Ulcer index and percentage of ulcer healing were evaluated to know the results. Compared to control group, PBE and ABE treated groups significantly reduced the ulcer index (P < 0.01 & P < 0.05, respectively) and percentage of ulcer healing was also similar to standard group. The study concluded that both the extracts of Boswellia serrata bark were effective in exhibiting anti-ulcer activity.

The effect of Frankincense in the treatment of moderate plaque-induced gingivitis: a double blinded randomized clinical trial
Samani MK, Mahmoodian H, Moghadamnia AA, Bejeh Mir AP, Chitsazan M
DARU J of Pharm Sci, 2011; 19(4): 288-294
The study evaluated the effect of Boswellia serrata extract (BE) and powder (BP) in the form of chewing gum on plaque-induced gingivitis in high school females. Periodontal surgery, scaling and root planning (SRP) was considered as one of the inclusion criteria. Six groups were made viz 1 and 2 with BE and BP, respectively, 3rd with no drug and no SRP, the 4th group with BE + SRP, the 5th group with BP + SRP and 6th group with only SRP. Different indices of periodontal examination were considered and groups 1 and 2 showed significant improvement (P < 0.001). Groups 4 and 5 showed the maximum decrease in gingival indices (P < 0.001) referring that Boswellia serrata could be an ideal supplement with SRP treatment. In conclusion, Boswellia serrata along with SRP is having superior results than SRP alone, which is the standard dental plaque removal treatment.

Boswellic Acid Suppresses Growth and Metastasis of Human Pancreatic Tumors in an Orthotopic Nude Mouse Model through Modulation of Multiple Targets
Park B, Prasad S, Yadav V, Sung B, Aggarwal BB
PLoS ONE, 2011; 6(10): e26943
The present study evaluated the anti-cancer properties of AKBBA extracted from Boswellia serrata. In-vivo study with orthotopic nude mouse model revealed that AKBBA was efficient in reducing tumour volume and in combination with gemcitabine, the regression was more significant compared to control (P < 0.01). Cell line (in-vitro) studies were conducted on four different pancreatic cancer cell lines and AKBBA was efficient in inducing apoptosis and sensitising the cancer cells to gemcitabine for apoptosis. Significant down-regulation on of Ki-67 (P < 0.05) compared to control indicates the inhibition of metastasis to other organ systems. Anti-inflammatory activity and down-regulation of multiple biomarkers like NF-κB, CXCR4, COX-2, MMP-9 and VEGF contributed to the anti tumour and metastatic inhibitory activity of AKBBA and in combination with gemcitabine effect was more significant. In conclusion, AKBBA potentiates the efficacy of gemcitabine by modulating multiple biomarkers of pancreatic cancer and inhibiting metastasis.

Hepatoprotective activity of Boswellia serrata extracts: in vitro and in vivo studies. Running Title: Hepatoprotective activity of Boswellia serrata extracts
Ibrahim M, ZeeyaUddin K and Narasu ML
J of Pharm App, 2011; 2(1):89-98
In this study, aqueous and chloroform extracts of leaf, gum, and bark of Boswellia serrata have been tested to know their hepatoprotective activity through in-vitro and in-vivo methods. Male albino rats have been used for the study and liver was aspirated from one animal for in-vitro studies. In in-vivo studies, Boswellia serrata extracts have been compared with control, paracetamol-treated (toxicant) and liv52-treated (standard) groups. In-vitro studies, extracts showed potent hepatoprotective activity by decreasing lactate dehydrogenase (LDH) and glutamate pyruvic transaminase (GPT) which indicates the minimal tissue damage. In in-vivo studies, aqueous extracts of leaf, bark, and gum were successful in decreasing biochemical parameters; aqueous leaf and bark extracts being effective compared with the standard. During histopathological evaluation aqueous leaf extract-treated group showed negligible necrosis and inflammation compared to other extracts, which showed minimal or mild cell damage. In conclusion extracts of Boswellia serrata were efficient in producing hepatoprotective activity.

Acetyl-11-keto-b-boswellic acid (AKBA); targeting oral cavity pathogen
Raja AF, Ali F, Khan IA, Shawl AS and Arora DS
BMC Research Notes, 2011; 4:406
The study evaluates the effect of Acetyl-keto-β-boswellic acid (AKBBA) on oral cavity pathogens Streptococcus mutans and Actinomyces viscosus. Minimum inhibitory concentration and minimum bactericidal concentrations of AKBBA were effective than other boswellic acids and thus it was studied further for bactericidal effect. Time kill kinetic study was significant (P < 0.05) when compared to control (ciprofloxacin) and at 16µg/ml concentration AKBBA completely compressed the emergence of mutants. This was considered as mutation prevention concentration of AKBBA. Post antibiotic effect of AKBBA was significantly higher compared to control (P < 0.05) and it also inhibited the formation of Streptococcus mutans and Actinomyces viscosus biofilms, effectively eradicating the preformed biofilms. In conclusion AKBBA can be a potent oral care agent and can be used in different dosage forms.

The antioxidant capacity and Anti-diabetic effect of Boswellia serrata triana and planch aqueous extract in fertile female diabetic rats and the possible effects on reproduction and histopathological changes in the Liver and Kidneys
Azemi ME, Namjoyan F, Khodayar MJ, Ahmadpour F, Padok AD, Panahi M
Jundishapur J Nat Pharm Prod. 2012; 7(4):168-175.
The study evaluated the anti-oxidant and anti-diabetic effect of aqueous extract of Boswellia serrata gum resin along with its effect on the liver, kidneys, and reproduction. Group 1 was healthy untreated rats, group 2 was diabetic control, and 3rd, 4th, 5th groups were diabetic rats treated with 200, 400 and 600 mg/kg boswellia extract, respectively. Ferric- reducing antioxidant power (FRAP) value was 0.99mm of Fe2+/L, which signifies the potent anti-oxidant activity of Boswellia serrata . A significant difference in blood glucose and HbA1C was seen in Boswellia treated groups (P < 0.01) when compared to diabetic control group. The most effective dose of boswellia extract was 200mg/kg (group 3). Histopathological study revealed that group treated with 200mg boswellia was showing normal liver and kidney tissues compared to other groups. Though resorbed embryo ratio was significant in the group treated with 200mg boswellia compared to diabetic control group (P < 0.001) a decrease in pregnancy rate was seen with all the boswellia-treated groups. The study concluded that appropriate doses of boswellia may effectively prevent diabetes-related complications in liver and kidney.

Boswellic acid induces epigenetic alterations by modulating DNA methylation in colorectal cancer cells
Shen Y, Takahashi M, Byun HM, Link A, Sharma N, Balaguer F, et al
Caner Bio Ther, 2012; 13(7): 542-552, DOI: 10.4161/cbt.19604
In this study, inhibition of demethylation by AKBBA was evaluated on different colorectal cancer (CRC) cell lines. Series of experiments were carried out to know the demethylation process induced by AKBBA. Apoptosis induction was evaluated by MTT assay and BrdU assay which showed 89-98% and 91-99% of cell death, respectively, in 40µM of AKBBA-treated group. In methylation microassay of SW48 cells, AKBBA treated group was significant in inducing demethylation compared to control group (P < 0.0001). Hierarchical clustering analysis showed up-regulation of genes responsible for tumor suppression where as with SW48 and SW480 cells marked inhibition of DNA methyl-transferase (DNMT) was seen in AKBBA treated group compared to control. The study concluded that AKBBA induced the demethylation and up-regulated the tumor suppressor genes which may contribute to anticancer activity of AKBBA in CRC cells.

Boswellic acid exerts antitumor effects in colorectal cancer cells by modulating expression of the let-7 and miR-200 microRNA family
Takahashi M, Sung B, Shen Y, Hur K, Link A, Boland CR, Aggarwal BB and Goel A
Carcinogenesis, 2012; 33(12): 2441–2449
Inhibition of tumor growth and cell invasion of colorectal cancer (CRC) by Acetyl-11-keto-β-boswellic acid (AKBBA) was evaluated in vitro and in vivo. in vitro , AKBBA (40 µM) showed a significant inhibition of cancer cell growth in both MTT assay (57-89% inhibition) and BrdU assay (41-85% inhibition). Colony formation assay showed a significant inhibition of clonogenic survival up to 92% with the 40µM concentration of AKBA. A dose-dependent apoptosis in CRC cells was observed with 20µM of AKBA showing maximum inhibition of 99% of migration and invasion. In RT-PCR up-regulation of let-7 and miR-200 family micro RNAs (mi-RNAs) was noticed, which suppress the tumor growth. This was further evaluated in-vivo in orthotopic CRC model. CRC-injected mice were given different doses of AKBBA for 28 days. There was a marked inhibition of tumor growth and distant metastasis observed which was dose-dependent. In addition to up-regulation of let-7 and miR-200, there was a significant down-regulation of their target genes, CDK6 and vimentin in the group treated with 200mg/kg AKBBA. The study concluded that AKBBA not only modulates mi-RNAs but also their target genes, thus exhibiting anti-tumor potential.

Diuretic Activity of Aqueous Extract of Boswellia serrata Roxb. Oleo Gum in Normal Albino Rats
Asif M, Atif M, Sulaiman SAS, Hassali MA , Shafie AA , Haq N and Saleem F
Val in Health, 2012; 15(7): A: 644
Diuretic activity of the aqueous extract of Boswellia serrata oleo gum was studied in vivo. Albino rats were divided into five groups viz, group 1 – treated with Normal saline, group 2 – treated with furosemide and groups 3, 4 and 5-treated with aqueous extract of Boswellia serrata oleo gum at 10, 30 and 50 mg/kg, respectively. Toxicity of the extract was also tested at the dose of 3000mg/kg. The group treated with 50mg Boswellia significantly increased the excretion of electrolytes and urine output compared to normal saline (P < 0.05). The lipschitz value was also positive for the diuretic activity of boswellia. There were no toxicity signs observed at 3000mg/kg dose of boswellia. In conclusion, the aqueous extract of Boswellia serrata oleo gum showed potent diuretic activity with no toxic effects.

In vitro Antioxidant and Free Radical Scavenging Activity of Different Extracts of Boerhavia diffusa and Boswellia serrata
Singh, Yadav IK, Chandra D and Jain DA
Int J of Pharm Sci and Research, 2012; 3(11):503-511
Aqueous and ethanolic extracts of Boswellia serrata were studied for their antioxidant property. Inhibition concentration at 50% (IC50) of the two extracts was determined with different free radical scavenging and reducing power assays. The IC50 of aqueous and methanolic extracts of Boswellia serrata gum were 23.53 and 91.97, respectively in DPPH scavenging assay, whereas at 69.67 µg/ml aqueous extract demonstrated lower IC50 value in nitric oxide radical scavenging assay compared to methanolic extract. Reducing power and phenolic assays also suggested that higher concentrations of aqueous extracts of Boswellia serrata gum could represent a better antioxidant property. Overall, aqueous extract of Boswellia serrata gum possessed a potent antioxidant activity and has application as natural antioxidant in different fields.

Boswellic acid inhibits growth and metastasis of human colorectal cancer in orthotopic mouse model by downregulating inflammatory, proliferative, invasive and angiogenic biomarkers
Yadav VR, Prasad S, Sung B, Gelovani JG, Guha S, Krishnan S and Aggarwal BB
Int J of Cancer, 2012; 130: 2176-2184
In this study, orthotopic colorectal cancer (CRC) mouse models were used to study the multiple targets of AKBBA from Boswellia serrata oleo gum resin. The human CRC cells were transferred to the mouse and studied for tumor growth, tumor volume, metastasis, ascites, proliferation and angiogenesis with a control group treated with only vehicle and other three groups treated with 50, 100 and 200mg of AKBBA. The group treated with 200mg AKBBA showed a significant inhibition of tumor growth and tumor volume compared to control (P < 0.001). Metastasis and ascites were significantly decreased in the group treated with 200 mg AKBBA (P < 0.001 in lungs, liver, and spleen). Proliferation and angiogenesis showed a significant inhibition of their biomarkers, Ki-67 and CD-31, respectively. Biomarkers of inflammation (cox2), proliferation (cyclin D1), invasion (MMP-9 & ICAM-1), angiogenesis (VEGF), and metastasis (CXCR4) were inhibited to the maximum in 200mg AKBBA-treated group, which confirms multiple targets of AKBBA in inhibition of human CRC tumor. Hence, AKBBA can be a potent natural agent in the treatment of CRC tumor growth and in suppression of distant metastasis.

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