Table 3.
Pharmacological effects of B. carterii.
| Models | Constituent/Extract | Mechanism | Reference |
|---|---|---|---|
| Anti-inflammatory effects | |||
| Adjuvant-induced arthritis in Lewis rats | Aqueous acetone extract | The extract significantly decreased arthritic scores, reduced paw oedema, and restrained the expression of TNF-α and IL-1β | [50] |
| 12-O-Tetradecanoylphorbol-13-acetate(TPA)-induced inflammation in specific pathogen-free female ICR mice | MeOH extract, n-hexane-soluble fraction EtOAc-soluble fraction, n-BuOH-soluble fraction H2O-soluble fraction β-Boswellic acid Acetyl-β-boswellic acid 11-Keto-β-boswellic acid Acetyl-11-keto-β-boswellic acid Acetyl-11α-methoxy-β-boswellic acid 9,11-Dehydro-β-boswellic acid Acetyl-9,11-dehydro-β-boswellic acid α-Boswellic acid Acetyl-α-boswellic acid Lupeolic acid Acetyl-lupeolic acid α-Elemolic acid Elemonic acid 3α-Hydroxytirucalla-7,24-dien-21-oic acid 3α-Acetoxytirucalla-7,24-dien-21-oic acid 3β-Hydroxytirucalla-8,24-dien-21-oic acid Incensole |
The H2O-soluble fraction and EtOAc-soluble fraction showed the strongest and the weakest anti-inflammatory effects in the fraction group, respectively. All compounds showed an anti-inflammatory effect | [38] |
| HeLa cells, 293T cells, RAW 264.7 macrophage cell, Jurkat T leukemia cells, 5.1 Jurkat and HeLa-Tat-Luc cell lines, A549 cells, human peripheral monocytes, female Sabra mice | Incensole acetate (IA) Incensole (IN) |
IA and IN (3-280 μM) inhibited IκBα degradation. IA inhibited IκBα and p65 phosphorylation by impairment of IKK activation and interfered with TAK/TAB-mediated phosphorylation of IKKα/β activation loop. IA inhibited NF-κB accumulation in cell nuclei and DNA binding, which may be related to its inhibition of gene expression by NF-κB | [51] |
| LPS-induced inflammatory in rat C6 glioma cell and human peripheral monocytes | Incensole acetate (IA) | 100 μmol/L IA, restraining the expression of IL-1b and TNF-α mRNA, inhibited the activation and mRNA level of NF-κB in human peripheral blood monocytes and C6 glioma cells | [52] |
| Lipopolysaccharide-activated mouse peritoneal macrophages | Olibanumol A Olibanumol B Olibanumol C Olibanumol H Olibanumol I 3,6-Dihydroxy-p-menth-1-ene p-menth-1-en-4α,6β-diol(-)-trans-sobrerol p-menth-4-en-1,2-diol p-Menth-5-en-1,2-diol Isofpuquierol Epilupeol |
Twelve compounds inhibited the production of NO | [10] |
| Lipopolysaccharide-activated mouse peritoneal macrophages | Olibanumol D Olibanumol E |
Two compounds exhibited nitric oxide production inhibitory activity | [18] |
| Carrageenan-induced paw oedema and Carrageenan-induced pleurisy in adult male CD1 mice and Wistar Han rats A549 cells and human whole blood |
α-Amyrin 3-O-Acetyl-β-boswellic acid 3-O-Acetyl-11-keto-β-boswellic acid β-Boswellic acid 11-Keto-β-boswellic acid 3-O-Oxalyl-11-β-keto-boswellic acid |
Human mPGES-1 was identified as one of the β-boswellic acid-binding proteins. The boswellic acid is capable of reversibly inhibiting the conversion of prostaglandin (PG) H2 to PGE2, which is mediated by mPGES-1. Besides, in A549 cells, boswellic acids restrained PGE2 generation, and in human whole blood, β-boswellic acid diminished PGE2 biosynthesis induced by LPS. β-boswellic acid (1 mg/kg) can inhibit pleurisy in rats, accompanied by decreasing levels of PGE2, and can also reduce paw oedema in mice | [35] |
| Cooperation-induced cerebral ischemic injury in C57BL/6 mice and TRPV 3-deficient mice | Incensole acetate (IA) | 0-50 mg/kg IA reduced the levels of TNF-α, IL-1β, and TGF-β, the activity of NF-κB, and the expression of GFAP in the brain of model mice in a dose-dependent manner | [53] |
| Formalin and carrageenan-induced paw oedema in mice and oxytocin-induced dysmenorrhea in mice | Water extract of frankincense (FWE) | FWE significantly inhibited PGE2 production, and 5.2 g/kg FWE inhibited nitrite production | [54] |
| Neutrophils, monocytes, and platelets from human blood | Lupeolic acid (LA) Acetyl-lupeolic acid (Ac-LA) Acetyl-hydroxy-lupeolic acid (Ac–OH–LA) |
Ac–OH–LA, which may directly hamper with cPLA2a activity (IC50 = 3.6 μM), lowered the biosynthesis of COX-, 5-LO-, and 12-LO-derived eicosanoids, with consistent IC50 value ranging from 2.3 to 6.9 μM. | [42] |
| A549 cells | 3-α-Hydroxy-8,24-dienetirucallic acid 3α-Acetoxy-8,24-dienetirucallic acid 3-β-Hydroxy-8,24-dienetirucallic acid 3-Oxo-8,24-dienetirucallic acid 3-α-Hydroxy-7,24-dienetirucallic acid 3α-Acetoxy-7,24-dienetirucallic acid Roburic acid 4, (23)-Dihydroroburic acid 4, (23)-Dihydro-11-keto-roburic acid Lupeolic acid 3-O-Acetyl-lupeolic acid 3-O-Acetyl-28-hydroxy-lupeolic acid |
Twelve compounds suppressed mPGES-1 with increased potencies. 3α-Acetoxy-7,24-dienetirucallic acid and 3α-acetoxy-8,24-dienetirucallic acid suppressed mPGES-1 activity with IC50 = 0.4 μM, each | [28] |
| Xylene-induced ear oedema model and formalin-inflamed hind paw model in Kunming mice | Frankincense oil extract (FOE) α-Pinene Linalool 1-Octanol |
FOE and three compounds restrained inflammatory infiltrates and COX-2 overexpression induced by the nociceptive stimulus | [55] |
| LPS-induced NO production in RAW 264.7 cell | Boscartol K Boscartol L Boscartol F |
Boscartol K, boscartol L, and boscartol F inhibited NO production. | [20] |
| LPS-induced NO production in RAW 264.7 cell | (rel)-(1S,5 R,7E,11 E)-1-Isopropyl-8,12-dimethyl-4-methylenecyclotetradeca-7,11-diene-1,5-diol 3-Oxo-tirucalla-8, 24-dien-21-oic acid 3β-Hydroxytirucalla-8,24-dien-21-oic acid 3-O-Acetyl-11-keto-boswellic acid |
Four compounds restrained NO production with IC50 values of 1.32, 3.04, 1.42, and 3.25 μM, respectively | [16] |
|
| |||
| Antioxidant effects | |||
| 5-Lipoxygenase | 3-O-Acetyl-9,11-dehydro-β-boswellic acid 3-O-Acetyl-11-methoxy-β-boswellic acid 9,11-Dehydro-β-boswellic acid |
Three compounds inhibited 5-LO activity to varying degrees, of which 3-O-acetyl-9,11-dehydro-β-boswellic acid almost completely abolished 5-LO activity | [28] |
| ABTS radical cation | Methanol extract | 1000 μg/kg extract exhibited a weak antioxidant activity | [56] |
|
| |||
| Antitumour effects | |||
| The human glioblastoma cells, U251 and U87-MG U87-MG-induced tumour model in BALB/c-nu nude mice |
3-O-Acetyl-11-keto-β-boswellic acid | 3-O-Acetyl-11-keto-β-boswellic acid, via the p21/FOXM1/cyclin B1 pathway, stop glioblastoma cells at the G2/M phase, which was related to the inhibition of mitosis through Aurora B/TOP2A pathway and the induction of mitochondrial-dependent apoptosis | [57] |
| LNCaP and PC-3 cell | Acetyl-keto-β-boswellic acid | 20 μg/ml acetyl-keto-β-boswellic acid induced apoptosis in LNCaP and PC-3 cell via a DR5 regulated pathway, which induced the expression of CAAT/enhancer-binding protein homologous protein | [58] |
| PC-3 cell MDA-MB-231 cell |
Acetyl-lupeolic acid | Directly bound to the pleckstrin homology domain, acetyl-lupeolic acid (0-20 μg/mL) advertised hindrance of phosphorylation of following targets of the Akt signalling pathway and nuclear accumulation of the mTOR target p70 ribosome and p65/NF-κB, β-catenin and c-Myc six protein kinase | [59] |
| B16F10 cell HT-1080 cell |
Boswellic acid acetate | In B16F10 cells, boswellic acid acetate (25 μM) inhibited cell migration activity, lured cell differentiation, blocked the cell population in the G1 phase, and restrained topoisomerase II activity. Boswellic acid acetate lured apoptosis of HT-1080 cells and prevented the secretion of MMPs from HT-1080 cells | [60] |
| Myeloid leukemia cells HL-60, U937, ML-1, erythrocyte leukemia cells DS-19 and K562 | BC-4, a mixture contained α- and β-boswellic acid acetate | In myeloid leukemia cells, BC-4 (24.2 μM) lured monocytic differentiation. BC-4 also increased specific and nonspecific esterases. Besides, BC-4 dose- and time-dependently inhibited growth of all cell lines tested | [31] |
| IMR-32, NB-39, and SK-N-SH cell |
β-Boswellic acid, acetyl-β-boswellic acid, 11-keto-β-boswellic acid, acetyl-11-keto-β-boswellic acid, acetyl-11α-methoxy-β-boswellic acid, 9,11-dehydro-β-boswellic acid Acetyl-9,11-dehydro-β-boswellic acid, acetylα-boswellic acid, lupeolic acid, acetyl-lupeolic acid, elemonic acid, 3α-hydroxytirucalla-7,24-dien-21-oic acid, 3α-acetoxytirucalla-7,24-dien-21-oic acid, incensole Incensole acetate |
In the above cells, these fifteen compounds exhibited potent cytotoxic activities | [21] |
| Text of activation of NOR1 | Acetyl-9,11-dehydro-β-boswellic acid Elemonic acid 3α-Hydroxytirucalla-7,24-dien-21-oic acid 3β-Acetoxytirucalla-7,24-dien-21-oic acid 3α-Hydroxytirucalla-8,24-dien-21-oic acid |
Five compounds indicated potent inhibitory effects of the activation of (-/+)-(E)-methyl-2[(E)-hydroxyimino]-5-nitro-6-methoxy-3-hexemide (NOR 1). | [21] |
| PC-3 cell | 3α-Acetyl-11-keto-α-boswellic acid | 3α-acetyl-11-keto-α-boswellic acid inhibited the proliferation of human PC-3 cells and induced apoptosis, as shown by the activation of caspase-3 and the induction of DNA fragmentation. Furthermore, 3α-acetyl-11-keto-α-boswellic acid inhibited the proliferation and induced apoptosis of PC-3 xenografted to the chorioallantoic membrane of the chicken chorioallantoic membrane. | [33] |
| Bladder cancer cell J82 Immortalized normal bladder cell UROtsa |
Frankincense essential oil (FEO) | FEO-activated signal of IL-6, histone core proteins, and heat shock proteins. FEO induced selective cancer cell death through NRF-2-mediated oxidative stress. | [61] |
| Jurkat cell | Boswellia water extract | Boswellia extract (200 μg/ml) promoted apoptosis of Jurkat cells and stopped cell differentiation in the G1 phase. | [62] |
| Bladder cancer cell J82 | Frankincense oil | Through activating genes responsible for cell apoptosis, cell growth inhibition, and cell cycle arrest, frankincense oil inhibited the cell viability of J82 cells, but cell death did not result in DNA fragmentation. | [63] |
| N-2A cells | Ethanol fraction of frankincense | Ethanol fraction showed cytotoxicity to neuro-2A cell with LC50 of 0.081 mg/mL. | [64] |
| Prostate cancer cells LNCaP and PC-3 | Acetyl-11-keto-β-boswellic acid | Based on the binding activity of Sp1, the active compound downregulated AR short promoter and hindered cellular proliferation. Luring p21 (WAF1/CIP1) and preventing cyclin D1 in cells, the compound (20-40 μM) induced G1 phase cell cycle arrest. | [65] |
| HT-29, HCT-116, SW480, and LS174 T colon cancer cell lines | 3-acetyl-11-keto-β-boswellic acid | 3-acetyl-11-keto-β-boswellic acid (30 μM) could activate the PI3K/Akt pathway. However, when we inhibited the PI3K pathway, the cell apoptosis induced by 3-acetyl-11-keto-β-boswellic acid would enhance | [66] |
| Hep-G2 cell | Verticilla-4(20),7,11-triene | Verticilla-4(20),7,11-triene showed an inhibitory effect against the proliferation of Hep-G2 cell line | [15] |
| PTEN-overexpressing PC-3 cells Peripheral blood mononuclear cells LNCaP cell PC-3 tumours xenografted to nude mice and chick chorioallantoic membranes |
3-Oxo-tirucallic acid 3-α-Acetoxy-tirucallic acid 3-β-Acetoxy-tirucallic acid |
Tirucallic acids inhibited Akt activity, downregulated the pathway of Akt activation, and induced apoptosis in prostate cancer cell lines. However, 3-β-acetoxy-tirucallic acid showed no significant activation of Akt1, which lacks the pleckstrin homology domain. The compounds inhibited the proliferation and induced apoptosis of tumours xenografted to the allantoic membrane of chicken veins, and postponed the progression of pre-established prostate tumours in nude mice without causing systemic toxicity | [22] |
|
| |||
| Antiviral effects | |||
| Hepatitis C virus | Boswellia carterii | B. carterii showed toxicity to the hepatitis C virus with IC50 of 23 mg/mL, which may be related to its inhibition of hepatitis C virus protease. | [67] |
| TPA-induced production of EBV-EA in Raji cell |
β-Boswellic acid Lupeolic acid Acetyl-lupeolic acid Elemonic acid 3α-Hydroxytirucalla-7,24-dien-21-oic acid 3α-Acetoxytirucalla-7,24-dien-21-oic acid 3β-Hydroxytirucalla-8,24-dien-21-oic acid |
In Raji cells, the above compounds show dose-dependent inhibition of EBV-EA induction induced by TPA | [21] |
|
| |||
| Antimicrobial effects | |||
|
Staphylococcus aureus (S. aureus) ATCC 29213 S. aureus ATCC 25923 S. aureus ATCC 43866 S. epidermidis DSM 3269 Escherichia coli (E. coli) ATCC 25922 Pseudomonas aeruginosa (P. aeruginosa) ATCC 9027 Candida albicans (C. albicans) ATCC 10231 C. tropicalis ATCC 13803 |
Oleo gum resin oil | The antibacterial activity of the oleo gum resin oils from B. carterii was identified and found to show antibacterial activity to the above bacterial | [68] |
| Trichosporon ovoides | Essential oil (EO) | EO showed antibacterial activity against trichosporon ovoides with MIC and MIF of 25 μl/ml and 50 μl/ml, respectively | [69] |
|
| |||
| Neuroprotective effects | |||
| The Sabra line mice were selected to be compliant for 10 generations. | Incensole acetate (IA) | IA has shown potent TRPV3 agonists, which caused anti-anxiety-like and anti-depression-like behavioural effects, with changes in c-Fos activation in the brain | [70] |
| Anterior cerebral artery ligation-induced cerebral ischemic injury in C57BL/6 mice and TRPV 3-deficient mice | Incensole acetate (IA) | 0-50 mg/kg IA dose-dependently reduced the cerebral infarction area and the contents of TNF-α, IL-1β, and TGF-β in the brain of the model mice, the activity of NF-κB, and the expression of GFAP in the brain. The behavioural assessment found that IA dose-dependently reduced nerve damage. Interestingly, IA showed only partial neuroprotective effects in TRPV3-deficient mice | [52] |
| LPS-induced inflammatory in rat C6 glioma cell and human peripheral monocytes | Incensole acetate (IA) | Incensole acetate (100 μmol/L) downregulated NF-κB activation and mRNA level in both human peripheral monocytes and C6 glioma cells. Moreover, it impaired the inflammatory reaction in human peripheral monocytes | [52] |
| Weight drop device-induced closed head injury in male Sabra mice | Incensole acetate (IA) | IA (50 mg/kg) alleviated inflammation and neurodegeneration in the hippocampus by inhibiting the mRNA level of TNF-α and IL-1β after closed head injury. Incensole acetate induced a mild hypothermic effect, but it did not affect tissue oedema formation | [52] |
| HEK293 cells, female Sabra mice, wild-type C57BL/6, and TRPV3(KO) female mice | Incensole acetate (IA) | IA (50 mg/kg) regulated the expression of c-Fos in mice brain areas, including that related to anxiety and depression. IA (500 μM) activated TRPV3 channels as determined by calcium imaging. IA activated a TRPV3 current in HEK293 cells and relieved depression and anxiety in wild-type but not in TRPV3 KO mice | [70] |
| The mice fed by breast milk which was generated from the Boswellia-fed mice | B. carterii | Pregnancy or lactation mother mice receiving B. carterii injection upregulated CaMKII mRNA in the hippocampus of offspring, but no significant change in hippocampal CaMKIV mRNA expression | [71] |
|
| |||
| Kidney protective effects | |||
| Oral adenine-induced chronic renal failure model in adult male albino rats ischemia-reperfusion injury-induced acute renal failure model in adult male albino rats | Boswellia | Prophylactic oral administration of Boswellia decreased serum urea, blood urea nitrogen, and the activity of C-reactive protein | [72] |
|
| |||
| Hepatoprotective effects | |||
| D-galactosamine-induced toxicity in HL-7702 cell | Boscartol A, boscartol B, boscartol C, boscartol E, boscartol F, boscartol H, and boscartol I | Seven compounds (10 μM) reduced cytotoxicity, which may be the basis of its liver protection | [19] |
| D-galactosamine-induced cytotoxic in HL-7702 cell | Acetyl-α-elemolic acid 3β-Hydroxytirucalla-8,24-dien-21-oic acid 3α-Hydroxytirucalla-8,24-dien-21-oic acid 3β-Hydroxy-mansumbin-13(17)-en-16-one |
Four compounds reduced cytotoxic and increased the survival rate in cell | [24] |
| D-galactosamine-induced toxicity in HL-7702 | Boscartin P, boscartin U, boscartin V, boscartin W, boscartin X, boscartin Y, boscartin AA, boscartin AB, boscartin AE, boscartin AF, incensole, incensole oxide acetate, incensole oxide, 1,4-epoxy-8,13-cembrandien-5,12-diol, 4,8-epoxy-8,12-cembrandien-5,12-diol | Fifteen compounds (10 μM) showed hepatoprotective effect against HL-7702 cell injury induced by D-galactosamine | [4] |
|
| |||
| Immunomodulatory effects | |||
| Th17 CD4+T cell, Th1, Th2, and Treg cell | Acetyl-11-keto-β-boswellic acid | Slightly increasing the differentiation of Th2 and Treg cells, acetyl-11-keto-β-boswellic acid (1 or 5 μM) reduced the differentiation of human CD4 (+) T cells. Further, acetyl-11-keto-β-boswellic acid reduced IL-17A released from memory Th17 cells triggered by IL-1β, which may involve IL-1β signalling by inhibiting the phosphorylation of IL-1 receptor-associated kinase 1 and STAT3 | [73] |
| Peripheral blood lymphocytes | Palmitic acid, lupeol, β-boswellic acid, 11-keto-β-boswellic acid, acetyl-β-boswellic acid, acetyl-11-keto-β-boswellic acid, acetyl-α-boswellic acid, 3-oxo-tirucallic acid, 3-hydroxy-tirucallic acid | Nine compounds promoted the transformation of peripheral blood lymphocytes | [12] |
| Murine splenocytes | Ethanol extract and sesame oil extract | Using ethanol as a solvent to deliver resin extracts resulted in significant cytotoxicity, which was not seen when ethanol was added alone. In contrast, when delivered by sesame oil solvent, resin extract dose-dependently inhibited TH1 cytokines and dose-dependently enhanced TH2 cytokines | [37] |
| Wister albino mice | Boswellia carterii smoke | The smoke resulted that alveolar capillaries were damaged, neutrophil nucleus contracted, mitochondria swelled and elongated in type 2 lung cells, type 2 lung cells were shed, most microvilli were shed, and leukocyte neutrophils were exuded in the alveolar cavity | [74] |
|
| |||
| Other effects | |||
| Epinephrine hydrochloride and cool water bath-induced acute cold blood model in SD rats | Stir-fried frankincense (SFF) Vinegar-processed frankincense (VPF) Frankincense oral administration (FRA) |
Frankincense (2.7 g/kg) presented more anticoagulant function than its processed products. FRA reduced the levels of DD and TAT and increased the content of PGI2. The processing of frankincense resulted in changes in its absorption and pharmacokinetics | [36] |
| Myeloid leukemia cells HL-60, U937, and ML-1, and erythrocyte leukemia cells DS-19 and K562 | Boswellic acid acetate | The compounds advertised a time- and dose-dependent induction and differentiation on myeloid leukemia cells expressed significant pro-apoptotic effects above 15 mg/ml. They also enriched the red blood cell line leukemia cells DS-19 and K562 at the G1 phase | [31] |
| Jurkat cell | Boswellia carterii Birdw. extract | Frankincense extract induced Jurkat cell apoptosis, promoted Jurkat cell apoptosis, and stopped cell differentiation at G1 phase | [74] |
| Myeloid leukemia cells NB4, SKNO-1, K562, U937, ML-1, and HL-60 | Boswellic acid acetate (BAA) | BAA, under the condition of 20 μg/ml for 24 h, decreased cell membrane potential, and p53 mutation did not affect the pro-apoptotic effect of boswellic acid acetate. Also, BCL-2, Bax, and Bcl-X do not participate in the process of BAA-induced cell membrane potential decline | [32] |
| Jack bean urease | 3-O-Acetyl-9,11-dehydro-β-boswellic acid 3-O-Acetyl-11-hydroxy-β-boswellic acid 3-O-Acetyl-11-keto-β-boswellic acid 11-Keto-β-boswellic acid |
Four compounds presented an inhibitory effect on Jack bean urease with IC50 of 6.27, 9.21, 16.34, and 85.23 μmol/L, respectively. The inhibitory force may be because of the formation of appropriate hydrogen bonds and the hydrophobic interaction between 3-O-acetyl-9,11-dehydro-β-boswellic acid and the urease active site | [43] |
| Callosobruchus chinensis (C. chinensis) and C. maculatus | B. carterii essential oil (BEO) | The essential oil showed toxicity to C. chinensis with LC50 and LC90 of 0.066 and 0.096 μL/mL, respectively. It expressed the same effect in C. maculatus with LC50 and LC90 of 0.050 and 0.075 μL/mL. BEO showed a concentration-dependent inhibitory effect on its spawning, growth, and development behaviour. It was found that the essential oil induced an increase in the levels of ROS, SOD, and CAT in pests. It also decreased the level of GSH and GSH/GSSG | [47] |
| Wistar male albino rats | Alcohol extract of olibanum | At a concentration of 1,000 μg/kg, the alcohol extract of olibanum, advertising dose-dependence NO-scavenging action, resulted in a marked increase in the serum levels of LDH, AST, and CK-MB, as well as MDA | [56] |
|
| |||
| Side effects | |||
| Male albino rat | Boswellic smoke | Histopathological sections and ultrastructure of the testis showed adverse effects on sperm development. Sperm analysis revealed that sperm counts, viability, and speed decreased in varying degrees, and the proportion of abnormal sperm increased | [75] |
| Wistar male albino rat | Boswellic smoke | The smoke resulted that fructose levels in epididymal fluid and prostate fluid were decreased. The histopathological sections and morphological analysis of the epididymis showed an adverse effect on sperm development | [75] |
| Wistar male albino rat | Boswellic smoke | The smoke caused a decrease in follicle-stimulating hormone, luteinizing hormone, testosterone and protein, sialic acid, and carnitine. Also, the smoke resulted in a decrease in sperm count, reduced vitality, and reduced speed. The testicular ultrastructure showed adverse changes to sperm | [76] |