Research highlights from 2013 to 2015

Antitumor efficacy of Boswellia serrata extract in management of colon cancer induced in experimental animal

Ahmed HH, Rahman MA, Salem FEZH, Shalby AB, Lokman MS
Int J Pharm Pharm Sci, 2013; 5(3): 379-389

The study evaluated the effect of Boswellia serrata methylene chloride extract (BMCE) on induced colon cancer. There were five groups viz; group 1- control (5%DMSO in saline), group 2 – cancer induced, group 3 – cancer induced + 5 – fluorouracil-treated, group 4 – cancer induced + low dose BMCE (1666.6mg/kg) and group 5 – cancer induced + high dose BMCE (3333.3mg/kg). Biochemical tests revealed that the enzymes responsible for invasion and metastasis like MMP-7, MMP-9, EGF, TGF-β, and TNF-α were significantly down-regulated by BMCE (P<0.05). Genes responsible for the carcinogenesis like β-catenin, K-ras and c-myc were also significantly down-regulated by BMCE when compared to both control and cancer groups (P<0.05). Histopathological reports of affected colon also supported the results by showing a decrease in inflammation and formation of new goblet cells in BMCE-treated groups. Boswellia was effective in combating the colon cancer induced in male rats.

Effect of Boswellia serrata on Alzheimer’s disease induced in rats

Yassin NAZ, El-Shenawy SMA, Mahdy KA, Gouda NAM, Marrie AEH, Farrag ARH and Ibrahim BMM
J Arb Soc Med Res, 2013; 8:1-11

This unique study evaluated the effect of Boswellia serrata aqueous infusion (BAI) on Alzheimer’s disease (AD) induced rats. There were 9 groups, which were divided into protective and therapeutic groups. Protective groups were given the standard drug rivastigmine and test drug BAI at 45 and 90 mg/kg before the administration of aluminum chloride (AlCl3) for the induction of AD. The therapeutic group was given the standard and test drugs after the administration of AlCl3 for 4 weeks. Activity box, T-maze, and rotarod tests showed a significant difference between drug-treated groups and, control and AlCl3 group (P<0.05). In the therapeutic group, BAI showed a significant result in a dose-dependent manner compared to control, AlCl3, baseline and BAI 45 mg-treated groups (P<0.05). There was a significant increase in the levels of acetylcholine and acetylcholinesterase in BAI-treated group (P<0.05). Histopathological changes also show that BAI-treated sections were similar to normal section. These results show that BAI can protect the brain from necrosis and deactivating effect of the AD; thus could be a promising active component in the treatment of the same.

Chemoprevention of intestinal adenomatous polyposis by acetyl-11-keto-beta-boswellic acid in APCMin/1 mice

Liu HP, Gao ZH, Cui SX, Wang Y, Li BY, Lou HX and Qu XJ
Int J Cancer, 2013; 132:2667-2681

The present study evaluated the chemopreventive efficacy of acetyl-11-keto-beta-boswellic acid (AKBBA) on adenomatous polyposis of small intestine and colon in APCMin/1 mice. Two groups were made where one was vehicle control (5% ethanol) and other was AKBBA-treated group (50 mg/kg) for 8 weeks. Chemoprevention was evaluated by prevention of adenoma formation, induction of apoptosis and prevention of angiogenesis. The AKBBA-treated group was significant in lowering the numbers of adenoma polyps in the small intestine (P<0.001) and, colon (P<0.005) and larger sized polyps were more targeted by AKBBA. There was significant increase in TUNEL positive cells (P<0.001) and apoptotic proteins like cleaved caspase-9 (P<0.01), caspase-3 (P<0.01) and Bax (P< 0.01) which indicate the induction of apoptosis. Prevention of angiogenesis was indicated by the reduction in microvascular density (MVD) by AKBBA (P<0.001). It also effectively reduced the inflammatory factors, which potentiates the chemo-preventive activity of AKBBA. The study concluded that AKBBA could be a potent active which can be used in the treatment of intestinal adenomatous polyposis.

Phytochemical analysis and antibacterial activity of Boswellia serrata against multi-drug resistant bacterial clinical isolates

Avasthi AS and Purkayastha S
IJBPAS, August, 2013, 2(8): 1691-1698

This study evaluated the in vitro antibacterial activity of Boswellia serrata against multidrug-resistant (MDR) bacterial isolates. Multiple fractions of Boswellia serrata gum resin were used for the study viz; n-hexane (n-hex) extract, dichloromethane (DCM) extract, ethyl -acetate (EtOAc) extract and aqueous extract. The phytochemical analysis confirmed the presence of flavonoids, alkaloids, steroids, cardiac glycosides, and triterpenoids. The antibacterial assessment showed that n-hex, DCM, and EtOAc extracts inhibited the growth of MDR Staphylococcus aureus and Enterococcus species effectively. Escherichia coli were also inhibited by n-hex and DCM extracts. The study concluded that the DCM and n-hex fractions of Boswellia serrata were found to be potentially bioactive against MDR bacteria.

A boswellic acid-containing extract attenuates hepatic granuloma in C57BL/6 mice infected with Schistosoma japonicum

Liu M, Chen P, Büchele B, Dong S, Huang D, Ren C, Zhang Y, Hou X, Simmet T & Shen J
Parasitol Res, 2013; 112: 1105–1111

The study evaluated the effect of water-soluble cyclodextrin complex preparation of Boswellia serrata oleo gum extract (BSE-CD) on hepatic granuloma caused by Schistosoma japonicum infection. The infected mice were divided into 4 groups viz; group 1 – no treatment, group 2- treated with cyclodextrin, group 3- treated with 140mg BSE-CD and group 4 – treated with 280mg/kg BSE-CD. After the completion of the study, mice were sacrificed and liver sections were studied for granuloma formation. Results showed a prominent decrease in granuloma in BSE-CD –treated groups. To evaluate the inflammatory changes and anti-granuloma effect, PGE2 and LTB4 levels were investigated which were significantly decreased in BSE-CD 280mg –treated group (P<0.05) and granuloma promoting protein MMP-9 was also significantly decreased (P<0.05) in BSE-CD –treated groups in a dose-dependent manner. Liver function indicators ALT and AST were also decreased significantly by BSE–CD 280mg (P<0.05), which confirms the hepatoprotective activity. The study concluded that BSE-CD can significantly decrease the granuloma size and inflammatory changes in Schistosoma japonicum infected mice.

Antibacterial activity of Boswellia serrata roxb. Ex colebr. ethanomedicinal plant against gram negative UTI pathogens

Patel NB and Patel KC
LifeSc leaflets, 2014; 53: 79-88

The present study evaluates the antibacterial efficacy of acetone, methanol, aqueous and petroleum ether extracts of Boswellia serrata on urinary tract infection (UTI) pathogens. This in vitro study involved estimation of minimal inhibitory concentration and zone of inhibition of extracts with gram negative bacteria viz; Escherichia coli, Pseudomonas aeruginosa, Proteus vulgaris and Klebesiella pneumonia. The aqueous extract was found to be the most potent with the minimal inhibitory concentration (MIC) 12.5 µg/µl, where as methanol, acetone and petroleum ether extracts showed good to moderate effects. The study concluded saying aqueous extract of Boswellia serrata possess highest inhibitory activity against gram negative bacteria causing UTI.

Effect of Boswellia serrata supplementation on blood lipid, hepatic enzymes and fructosamine levels in type2 diabetic patients

Ahangarpour A, Heidari H, Fatemeh RAA, Pakmehr M, Shahbazian H, Ahmadi I, Mombeini Z and Mehrangiz BH
J Dia Met Dis, 2014; 13:29

This study evaluated the effect of gum resin of Boswellia serrata(BS) on the blood parameters indicating the lipid variables and hepatic enzymes in 60 patients with type 2 diabetes. There were two groups, intervention group (received 900mg/day BS) and control group (did not receive the any drug). After 6 weeks of study, it was found that BS increased high density lipoprotein (HDL) significantly (P<0.05) and decreased low density lipoprotein (LDL – P<0.05), total cholesterol (P<0.05), serum glutamic oxaloacetic transaminase (SGOT -P<0.001), serum glutamic pyruvic transaminase (SGPT – P<0.01) and fructosamine (P<0.05) compared to baseline. Compared to control, there was significant decrease in very low density lipoprotein (VLDL – P<0.05), triglycerides (TG – P<0.05), total cholesterol (TC – P<0.01) and SGOT (P<0.01). The study concludes that daily supplementation of BS will help to manage the risk factors related to type 2 diabetes effectively.

Effect of Boswellia serrata extracts on degenerative Osteoarthritis in vitro and in vivo models

Nam DE, Kim OK, Shim TJ, Kim JH and Lee
J Korean Soc Food Sci Nutr, 2014; 43(5): 631-640

The present study evaluated the effects of Boswellia serrata extract (BW) in vitro on rat cartilage cells and in vivo on osteoarthritis (OA) induced rats. in vitro study revealed that the cell survival was elevated by BW at the concentration of 20µg/ml and, it also decreased the production of pro-inflammatory factors and activity of 5-lipoxygenase. in vivo study carried out for 35 days at the concentrations of 100 and 200mg showed the decrease in severity of OA and decrease in metalloproteinases which causes inflammation and degeneration. Significant protective effect was induced by BW at the concentration of 200mg. The study concluded that BW can effectively be used as therapeutic agent in degenerative OA.

Boswellia serrata extract attenuates inflammatory mediators and oxidative stress in collagen induced arthritis

Umar S, Umar K, Sarwar AHMG, Khan A, Ahmad N, Ahmad S, Katiyar CK, Husain SA and Khan HA
Phytomedicine, 2014; 21: 847-856

This study evaluated the effect of Boswellia serrata extract (BSE) on inflammatory mediators and oxidative stress in collagen induced arthritis (CIA) model for 21 days. There were 4 groups viz; control, CIA, CIA+BSE (100mg) and CIA+BSE (200mg), where last two arthritic groups were treated with mentioned concentrations of BSE, respectively. Biochemical studies showed significant reduction in articular elastase (P<0.001), myeloperoxidase (MPO – P<0.001), lipid peroxidase (LPO – P<0.001), and nitric oxide (NO – P<0.001), and there was significant restoration in glutathione (GSH – P<0.01) and superoxide dismutase (SOD – P<0.01), compared to CIA group. Inflammatory mediators also showed significant decrease in their levels compared to CIA group {IL-1β (P<0.001), IL-6 (P<0.001), TNF-α (P<0.001), INF-ɣ (P<0.01) and PGE2 (P<0.01)}. Histopathological studies showed minimal necrotic lesions in the sections of BSE-treated groups. Study concluded that BSE can be a potent phyto-medicine for chronic inflammatory conditions like arthritis.

Boswellia serrata suppresses colorectal carcinogenesis: In vitro and In vivo studies

Ahmed HH, Hamza AH, El-Toumy SA and Hassan AZ
Int J Pharm Sci Rev Res, 2014; 25(2): 51-61

This study was intended to evaluate the anti cancer activity of methanolic (BME) and methylene chloride (BMCE) extracts of Boswellia serrata in colorectal cancer induced rats. In vitro MTT assay showed that different concentrations of BME and BMCE significantly inhibited the proliferation of cancer cells (P<0.05). In vivo study showed that the levels of carcinoembryogenic antigen (CEA) and serum matrix metalloproteinase (MMP-7) were also significantly decreased compared to cancer group (P<0.05) and there was an insignificant decrease in transforming growth factor – β (TGF-β). On the contrary, colon cancer specific antigen – 4 (CCSA-4) was increased which confirms the anticancer activity of BME and BMCE against colon cancer. Apoptotic markers cytochrome – C (CYT – C) and programmed cell death protein – 4 (PDCDP – 4) were increased in boswellia-treated group compared to cancer group (P<0.05) signifying the induction of apoptosis. Proteins Cox-2, survivin and cyclin –D which may contribute to the malignancy, inhibition of apoptosis and tumerigenesis, respectively, were decreased in boswellia-treated group compared to cancer group. The study concluded that Boswellia serrata could be a promising chemo-preventive agent.

Boswellia serrata preserves intestinal epithelial barrier from oxidative and inflammatory damage

Catanzaro D, Rancan S, Orso G, Dall’Acqua S, Brun P,Cecilia Giron MC, Carrara M, Castagliuolo I, Ragazzi E, Caparrotta L, Montopoli M
Plos One, 2015; 10(5): e0125375

In this study Boswellia serrata extract (BSE) and AKBBA were tested on Caco-2 cells for affect on intestinal barrier integrity and cell permeability produced by inflammatory stimuli and reactive oxygen substance (ROS) generation. The cells were incubated with 500µM H2O2 for 24 hours and were made to produce ROS. Four groups were made viz, group 1 – control; group 2 – treated with 0.1µg/ml BSE, group 3 – treated with 1 µg/ml BSE and group 4 – treated with AKBBA. The difference between control and BSE and AKBBA groups in altering trans-epithelial electrical resistance (TEER) was significant (BSE – P<0.003 and AKBBA – P<0.0043) which showed that both BSE and AKBBA preserved intestinal barrier integrity. Pre-treatment with BSE and AKBBA significantly counteracted para-cellular permeability (P<0.0001) and NF-κB phosphorylation induced by oxidative and inflammatory stimuli (P<0.001) compared to H2O2 – treated group. There was also decrease in basal ROS and significant counteraction of ROS generation (P< 0.05) by BSE and AKBBA. The study concluded stating BSE or AKBBA could be effective medications in irritable bowel diseases, where intestinal epithelial regeneration is a challenge.

Boswellia serrata oleo- gum resin: A natural remedy for retrogradation of liver fibrosis in rats

Ahmed HH, El-Alfy NZ, Mahmoud MF and Yahya SMM
Der pharmacia letter, 2015; 7(1): 134-144

The present study evaluated the hepatoprotective effects of methylene chloride extract of Boswellia serrata (BSMC) on rats with thioacetamide induced liver fibrosis. The rats were divided into four groups viz, group 1- negative control, group 2- TAA-treated (positive control), group 3- BSMC 175mg –treated (BSMC control) and group 4- BSMC-treated for 8 weeks followed by TAA-treated for 7 weeks. There was significant decrease in liver function test parameters, serum aspertate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP) and bilirubin compared to TAA group (P<0.05). There was significant increase in glutathione (antioxidant), serum fibrinogen and hepatocyte growth factor (HGF) (P<0.05) which signifies the healing and growth of new liver tissue. Genes NQO1 and BCL-2, which regulates anti-oxidative stress and apoptosis, were also significantly increased by BSMC (P<0.05) which indicates the reversal of fibrosis of liver. Histopathological studies supported these data by showing minimal infiltrated inflammatory cells in sections of BSMC –treated groups. The study concluded that Boswellia serrata can be a potent phyto-medicine for hepatoprotective action.

Pretreatment with β-Boswellic acid improves blood stasis induced endothelial dysfunction: role of eNOS activation

Wang M, Chen M, Ding Y, Zhu Z, Zhang Y, Wei P, Wang J, Qiao Y, Li L, Li Y and Wen A
Scientific reports, 2015; 5:15357

This study evaluated the effect of β-boswellic acid (β-BA) on the endothelial dysfunction induced by the blood stasis in carotid artery blood stasis rat models and human umbilical vein endothelial cells (HUVECs). The treatment group was pre-treated with β-BA and investigations were carried out to know the effect. It was observed that, β-BA significantly decreased the co-agulation parameters in serum like fibrinogen. In models, β-BA significantly increased nitric oxide, which plays an important role in maintaining blood homeostasis and increased the phosphorylation of enzyme nitric oxide synthase (e-NOS), which regulates the production of NO. A significant increase in e-NOS phosphorylation and cell viability in OGD –treated HUVECs was observed by the treatment of β-BA. This also prevented vascular dilatation by endothelial protective activity of β-BA. Histological studies also supported the data by showing minimal areas where endothelium was broken. The study concluded that β-BA can prevent cell injury by blood stasis with its endothelial protective activity.

Effect of Boswellia serrata gum resin on the morphology of hippocampal CA1 pyramidal cells in aged rat

Hosseini-sharifabad M and Esfandiari E
Anat Sci Int, 2015; 90: 47–53

In this study, the effect of Boswellia serrata gum resin (BS) on morphology of superior region of cornu ammonis (CA1) in aged rats was studied. There were two groups, experimental (treated with BS 100mg) and control (given same amount of water). The sections of CA1 revealed that there were significant increase in the volumes of stratum pyramidalae and stratum radiatum, and in the dendritic segments in BS-treated group (P<0.05 with both parameters) compared to control group. There was also 20% increase in the total dendritic length and dendritic intersections showed a significant increase in number of circles in BS-treated group (P<0.05). These results convey that BS can potentially bring out morphological changes in CA1. Study concludes that BS is having a significant and effective neuro-protective activity.

Post-treatment with 11-Keto-β-Boswellic acid ameliorates cerebral ischemia–reperfusion injury: Nrf2/HO-1 pathway as a potential mechanism

Yi Ding Y, Chen M, Wang M, Li Y & Wen A
Mol Neurobiol, 2015; 52: 1430–1439

This study evaluated the effect of post-treatment of AKBBA on cerebral ischemia induced in Sprague dawly rats. Three groups were made; group 1 – control (no treatment), group 2 – ischemic reperfusion (I/R) + vehicle-treated and group 3 – I/R + AKBBA-treated. Sections of ischemic brain revealed the significant reduction of pale area (ischemic area) in AKBBA –treated group compared to vehicle group (P<0.05). Similarly neurological deficit also showed significant decrease in AKBBA-treated group (P<0.05). TUNEL staining showed the significant reduction of DNA damage by 4.4% in AKBBA group. Superoxide dismutase (SOD), and glutathione peroxidase (GPX) were significantly increased (P<0.05) and malondialdehyde (MDA) which signifies lipid peroxidase was significantly decreased (P<0.05) in AKBBA –treated group, denoting lowered oxidative stress. Western blot and immunoflouroscence revealed the increase in number of cells labelled Nrf2 and HO-1, which inhibited cell death and increase in oxidative stress. The study concludes that AKBBA has protective effect against cerebral ishchemia.

Protective effect of boswellic acids versus pioglitazone in a rat model of diet-induced non-alcoholic fatty liver disease: influence on insulin resistance and energy expenditure

Zaitone SA, Barakat BM, Bilasy SE, Fawzy MS, Abdelaziz EZ and Farag NE
Naunyn-Schmiedeberg's Arch Pharmacol, 2015; 388: 587–600

The present study evaluates the effect of boswellic acids (BA) on high fat diet induced fatty liver disease. Five groups were made viz; group 1 – normal palatable diet (NPD), group 2- high fat diet (HFD) for 12 weeks, group 3 – HFD+ pioglitazone 10mg, group 4 – HFD + BA 125mg and group 5 – HFD + BA 250mg. Groups treated with BA showed significant reduction in weight gain compared to HFD group, which was potentiated by significantly decreased liver and adiposity indices (P<0.05) and significant reduction in daily food intake (P<0.05) in BA- treated groups. Significant efficacy was shown by BA-250mg –treated group compared to pioglitazone –treated group (P<0.05). Significant down-regulation of TNF-α, IL-6, Cox-2 and lipid peroxidase was seen in BA-treated groups compared to HFD groups and BA-250mg was significantly better than pioglitazone (P<0.05). Fasting blood sugar, Insulin and HOMA-IR index were significantly reduced by BA compared to HFD group (P<0.05). Lipid profile was significantly improved by BA (P<0.05) and there was significant down-regulation of fat oxidation promoting enzyme CPT-1 in BA-treated groups. Sections of liver supported these data by showing significant reduction in optical density of oil red-o in BA-treated groups, indicating less accumulation of fat compared to HFD (P<0.05). Study concluded that BA can be an effective medication for diet induced non-alcoholic fatty liver disease and could be helpful in treating metabolic disorders.