Research highlights 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 Dec;2(2):92-8

The present study evaluated the anti-arthritic property of n-hexane extract of Boswellia serrata gum resin in male albino rats. The methanolic extract of Glycyrrhiza glabra was administered orally at a dose of 150 mg/kg and the n-hexane extract of Boswellia serrata was administered 50mg/kg bw for 21 days to the experimental animals after the induction of adjuvant arthritis. Further, the combined formulation containing both Glycyrrhiza glabra and Boswellia serrata 100 mg/kg was administered in a separate group. The anti-arthritic activity of Glycyrrhiza glabra and Boswellia serrata were assessed by a significant reduction of paw edema volume and it’s capacity to stabilize lysosomal enzyme activity such as ACP. The study concluded that the combined formulation containing both Glycyrrhiza glabra and Boswellia serrata at proportion (1:1) showed significant synergistic action and thus it maybe tried for therapeutic use clinically.

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):1-9

This study evaluated the antimicrobial activities of boswellic acids and further explored the time-kill potential, postantibiotic effect and biofilm susceptibility of acetyl–keto–β-boswellic acid (AKBBA) the most potent constituent of the boswellic acids; AKBBA MIC ranged from 2-8 µg/mL. The antibacterial mode of action of AKBBA might be due to the disruption of microbial membrane structure as confirmed in the popiodium iodide-leakage tests. The study concluded 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 (250 mg/kg) and aqueous (250 mg/kg) extracts of the bark of Boswellia serrata. Compared to the control group, Boswellia bark extracts treated groups showed significantly reduced the ulcer index and the percentage of ulcer healing were also similar to the standard group. The study concluded that both the extracts of b.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

KhosraviSamani M, Mahmoodian H, Moghadamnia A
PoorsattarBejeh Mir A, Chitsazan M. Daru.2011;19(4):288-94

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 planing (SRP) was considered as one of the inclusion criteria. Different indices of periodontal examination were assessed and the data revealed that Boswellia along with SRP produced remarkable mitigation of inflammatory indices. There was no difference in the outcome with the form of Boswellia administered, power or extract. Finally, the study concluded that Boswellia is a safe and cost-effective supplement with SRP treatment because Boswellia 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 described the anti-cancer properties of AKBBA from Boswellia serrata. Invivo study with the orthotopic nude mouse model revealed that AKBBA (100 mg/kg P.O.) was efficient in reducing tumor volume and in combination with gemcitabine, the regression was more significant compared to control (P<0.01). in vitro studies revealed that AKBBA was efficient in inducing apoptosis and sensitizing the cancer cells to gemcitabine for apoptosis. The significant down-regulation 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 antitumor and metastatic inhibitory activity of AKBBA and the effect was more significant in combination with gemcitabine. Finally, the study concluded that 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.

Ibrahim M, Uddin KZ, Narasu ML
International Journal of Pharmaceutical Applications. 2011;2(1):89-98

This study evaluated the hepatoprotective activity of Boswellia serrata leaves, gum, and bark aqueous and chloroform extracts. Both in vitro (using primary rat hepatocytes monolayer culters) and in vivo (using male albino rats) results demonstrated the protective activity of Boswellia serrataextracts against the paracetamol-damage. Boswellia extracts improved the serum biomarker of liver damage. The study concluded that the extracts of Boswellia serrata have hepatoprotective activity.

Hepatoprotective activity of Boswellia serrata extracts: in vitro and in vivo studies.

Ibrahim M, Uddin KZ, Narasu ML
International Journal of Pharmaceutical Applications. 2011;2(1):89-98

This study evaluated the hepatoprotective activity of Boswellia serrata leaves, gum, and bark aqueous and chloroform extracts. Both in vitro (using primary rat hepatocytes monolayer culters) and in vivo (using male albino rats) results demonstrated the protective activity of Boswellia serrataextracts against the paracetamol-damage. Boswellia extracts improved the serum biomarker of liver damage. The study concluded that the extracts of Boswellia serrata have hepatoprotective activity.

Acetyl-11-keto-b-boswellic acid (AKBBA); targeting oral cavity pathogen

Raja AF, Ali F, Khan IA, Shawl AS, Arora DS
BMC Research Notes.2011;4:406

The study evaluated 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 a bactericidal effect. Time kill kinetic study was significant (P<0.05) when compared to control (ciprofloxacin) and at 16µg per mL concentration AKBBA completely compressed the emergence of mutants. This was considered as a mutation prevention concentration of AKBBA. Postantibiotic 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 eradicated the preformed biofilms. It concluded that 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 Histological Changes in the Liver and Kidneys

Azemi ME, Namjoyan F, Khodayar MJ, Ahmadpour F, Padok AD,
Panahi M Jundishapur J Nat Pharm Prod. 2012 Fall;7(4):168-75

The study evaluated the antioxidant and antidiabetic effect of aqueous extract of Boswellia serrata gum resin along with its effect on the liver, kidneys, and reproduction in rats. Animals were divided into five groups, diabetic rats were treated with 200, 400 and 600 mg/kg Boswellia extract. Boswellia-treated group animals showed significantly different blood glucose and HbA1C values (P<0.01), normal liver and kidney tissues, and potent antioxidant activity -ferric-reducing antioxidant power (FRAP) value was 0.99mm of Fe2+/Lcompared to control group diabetes animals. The most effective dose of Boswellia extract was found to be 200 mg/kg. Although the resorbed embryo ratio was significant in animals treated with 200 mg/kg Boswellia (P<0.001), a decrease in pregnancy rate was seen with all the Boswellia-treated animals. 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
Leung HC, Boland CR, Goel A Cancer Biol Ther. 2012 May;13(7):542-5

This study evaluated the inhibition of demethylation by AKBBA in different colorectal cancer (CRC) cell lines. A 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 the control group (P<0.0001). Hierarchical clustering analysis showed the up-regulation of genes responsible for tumor suppression,and marked inhibition of DNA methyl-transferase (DNMT) was seen in the SW48 and SW480 cells treated with AKBBAcompared to control. The study concluded that AKBBA induced the demethylation and up-regulated the tumor suppressor genes, which may contribute to the 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,
Goel A Carcinogenesis. 2012 Dec;33(12):2441–9

The inhibition of tumor growth and cell invasion of colorectal cancer (CRC) by Acetyl-11-keto-β-boswellic acid (AKBBA) was evaluated both in vitro and in vivo. AKBBA (40 µM) showed significant inhibition of cancer cell growth in both MTT (57–89% inhibition) and BrdU assays (41–85% inhibition), and significant inhibition of clonogenic survival (up to 92%), in vitro.AKBBA (20µM) showed dose-dependent apoptosis in CRC cells with andinhibited 99% of migration and invasion. Further, the in vivo evaluation in the orthotopic model was carried out using CRC-injected mice treated with different doses of AKBBA for 28 days. Dose-dependent marked inhibition of tumor growth and distant metastasis was observed. In addition, up-regulation of let-7 and miR-200, as well as significant down-regulation of their target genes, CDK6 and vimentin were noted with AKBBA. With these results, the study concluded that AKBBA not only modulates miRNAs but also their target genes, thus contributing 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,
Saleem F Val in Health, 201215(7):A: 644

Diuretic activity of the aqueous extract of Boswellia serrata oleo gum was studied in albino rats.Animals were divided into five groups, aqueous extract of Boswellia serrata oleo gum was administered to three groups of animals at doses10, 30 and 50 mg/kg. The group treated with 50mg Boswellia significantly increased the excretion of electrolytes and urine output compared to the normal saline-treated group (P<0.05). The Lipschitz value was also positive for the diuretic activity of Boswellia. Toxicity of the extract was also tested up to the dose of 3000mg/kg and there were no toxicity signs observed. The study concluded that the aqueous extract of Boswellia serrata oleo gum had potent diuretic activity with acceptable tolerability.

In vitro Antioxidant and Free Radical Scavenging Activity of Different Extracts of Boerhaviadiffusa and Boswellia serrata

Singh HP, Yadav IK, Chandra D, Jain DA
International Journal of Pharm Sciences and Research. 2012;3(11):503-11

In this study, aqueous and ethanolic extracts of Boswellia serrata were studied for their antioxidant properties. In DPPH scavenging assay, the IC50 values of aqueous and methanolic extracts of b.serrata gum were 23.53 and 91.97µg per mL, respectively, whereas,the aqueous extract demonstrated lower IC50 value in nitric oxide radical scavenging assay (69.67 µg per mL)compared to methanolic extract. Reducing power and phenolic assays also suggested that higher concentrations of aqueous extracts of B. serrata gum could represent a better antioxidant property. Overall, the aqueous extract of b.serrata gum possessed a potent antioxidant activity and has application as a 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, Aggarwal BB
Int J Cancer. 2012 May;130(9):2176-84

In this study, orthotopic colorectal cancer (CRC) mouse model was used to study the multiple targets of AKBBA from Boswellia serrata oleo gum resin. The human CRC cells were transferred to the mouse. The tumor growth, tumor volume, metastasis, ascites, proliferation and angiogenesis in control group (treated with only vehicle) and other three groups treated with 50, 100 and 200mg of AKBBA were studied. The group treated with 200mg AKBBA showed 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 significant inhibition of their biomarkers, Ki-67 and CD-31, respectively. Biomarkers of inflammation (COX-2), 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 the suppression of distant metastasis.