PMID: 

Oncotarget. 2019 May 28 ;10(37):3472-3490. Epub 2019 May 28. PMID: 31191820

Abstract Title: 

Frankincense essential oil suppresses melanoma cancer through down regulation of Bcl-2/Bax cascade signaling and ameliorates heptotoxicity via phase I and II drug metabolizing enzymes.

Abstract: 

Melanoma is a deadly form of malignancy and according to the World Health Organization 132,000 new cases of melanoma are diagnosed worldwide each year. Surgical resection and chemo/drug treatments opted for early and late stage of melanoma respectively, however detrimental post surgical and chemotherapy consequences are inevitable. Noticeably melanoma drug treatments are associated with liver injuries such as hepatitis and cholestasis which are very common. Alleviation of these clinical manifestations with better treatment options would enhance prognosis status and patients survival. Natural products which induce cytotoxicity with minimum side effects are of interest to achieve high therapeutic efficiency. In this study we investigated anti-melanoma and hepatoprotective activities of frankincense essential oil (FEO) in bothandmodels. Pretreatment with FEO induce a significant (

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PMID: 

Turk J Med Sci. 2019 08 8 ;49(4):1033-1040. Epub 2019 Aug 8. PMID: 31317694

Abstract Title: 

Effect of 4 weeks of frankincense consumption on explicit motor memory and serum BDNF in elderly men

Abstract: 

Background/aim: Memory is a mechanism for coding, storing, and recalling information. Weak memory and learning disability are common psychological problems in the elderly. The aim of this study was to investigate the effect of 4 weeks of frankincense consumption on explicit motor memory and serum BDNF in the elderly.Materials and methods: Twenty elderly men (mean age of 60.2± 1.7 years) were randomly divided into two groups: experimental (n = 12) and placebo (n = 8). The first blood samples were collected 24 h before the pretest. Then both groups participated in a 4-week exercise program based on the protocol of exercising motor memory. During this period,the experimental group received 500-mg frankincense pills two times a day. The second blood sample collection and acquisition test were conducted following the last session of the exercise program. A retention test and a third blood sampling were performed 2 weeks after the last training session. Mixed analysis of variance (2 × 3) for repeated measures was used to analyze the data.Results: Intergroup comparisons showed that frankincense had a significant effect on the acquisition and retention of explicit motor memory. No difference was observed in serum BDNF between the experimental and placebo groups.Conclusion: This study revealed that 4 weeks of frankincense consumption facilitates the acquisition and retention of motor memory in older men with moderate mental status.

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PMID: 

Molecules. 2019 Aug 24 ;24(17). Epub 2019 Aug 24. PMID: 31450584

Abstract Title: 

Seeing the Unseen of the Combination of Two Natural Resins, Frankincense and Myrrh: Changes in Chemical Constituents and Pharmacological Activities.

Abstract: 

For the treatment of diseases, especially chronic diseases, traditional natural drugs have more effective therapeutic advantages because of their multi-target and multi-channel characteristics. Among many traditional natural medicines, resins frankincense and myrrh have been proven to be effective in the treatment of inflammation and cancer. In the West, frankincense and myrrh have been used as incense in religious and cultural ceremonies since ancient times; in traditional Chinese and Ayurvedic medicine, they are used mainly for the treatment of chronic diseases. The main chemical constituents of frankincense and myrrh are terpenoids and essential oils. Their common pharmacological effects are anti-inflammatory and anticancer. More interestingly, in traditional Chinese medicine, frankincense and myrrh have been combined as drug pairs in the same prescription for thousands of years, and their combination has a better therapeutic effect on diseases than a single drug. After the combination of frankincense and myrrh forms a blend, a series of changes take place in their chemical composition, such as the increase or decrease of the main active ingredients, the disappearance of native chemical components, and the emergence of new chemical components. At the same time, the pharmacological effects of the combination seem magically powerful, such as synergistic anti-inflammation, synergistic anticancer, synergistic analgesic, synergistic antibacterial, synergistic blood-activation, and so on. In this review, we summarize the latest research on the main chemical constituents and pharmacological activities of these two natural resins, along with chemical and pharmacological studies on the combination of the two.

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PMID: 

Iran J Pharm Res. 2019 ;18(2):877-886. PMID: 31531070

Abstract Title: 

Beta-Boswellic Acid and Ethanolic Extract of Olibanum Regulating the Expression Levels ofandGenes.

Abstract: 

Physiological studies confirm improvement of memory by Olibanum, a resin fromspecies, while little is known about the molecular mechanism by which it affects memory performance. Two master transcription factors, CREB-1 and CREB-2, regulate downstream memory-related genes expression, leading to the long-term memory potentiation. This study addresses the effects of Beta-boswellic acid (β-BA), the main ingredient of Olibanum, and ethanolic extract of the resin fromon the expression ofandgenes in B65 cell line. B65 cells were treated withβ-BA or ethanolic extract of Olibanum in different doses and time intervals and the cell viability/toxicity was measured by MTT assay. Total RNA was extracted from the treated and untreated control cells and cDNA was synthesized. The expression levels ofandgenes were quantified by Real-time PCR. MTT assays revealed 50% inhibitory concentrations of 42.05, 29.63, and 21.78μg/mL for ethanolic extract of Olibanum and 89.54, 44.05, and 21.12 µM for β-BA at 24, 48, and 72 h time intervals respectively. Both β-BA and ethanolic extract of Olibanum alteredandgene expression levels in time-dependent but not in dose-dependent way. However,β-BA showed stronger and more stable effects. The expression levels of the both genes followed an alternate upregulation and downregulation pattern, but in opposite directions, in response to the both solutions with the progress of time. These results suggest that Olibanum possibly improves memoryperformance, at least partially, by regulating the levels of CREB-1 and CREB-2 transcription factors via positive/negative-feedback loops.

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PMID: 

Nutrients. 2019 Oct 2 ;11(10). Epub 2019 Oct 2. PMID: 31581678

Abstract Title: 

Comparative Investigation of Frankincense Nutraceuticals: Correlation of Boswellic and Lupeolic Acid Contents with Cytokine Release Inhibition and Toxicity against Triple-Negative Breast Cancer Cells.

Abstract: 

For centuries, frankincense extracts have been commonly used in traditional medicine, and more recently, in complementary medicine. Therefore, frankincense constituents such as boswellic and lupeolic acids are of considerable therapeutic interest. Sixteen frankincense nutraceuticals were characterized by high-performance liquid chromatography with tandem mass spectrometry (HPLC-MS/MS), revealing major differences in boswellic and lupeolic acid compositions and total contents, which varied from 0.4% to 35.7%. Frankincense nutraceuticals significantly inhibited the release of proinflammatory cytokines, such as TNF-α, IL-6, and IL-8, by LPS-stimulated peripheral blood mononuclear cells (PBMC) and whole blood. Moreover, boswellic and lupeolic acid contents correlated with TNF-α, IL-1β, IL-6, IL-8, and IL-10 inhibition. The nutraceuticals also exhibited toxicity against the human triple-negative breast cancercell lines MDA-MB-231, MDA-MB-453, and CAL-51 in vitro. Nutraceuticals with total contents of boswellic and lupeolic acids>30% were the most active ones against MDA-MB-231 with a half maximal inhibitory concentration (IC)≤ 7.0 µg/mL. Moreover, a frankincense nutraceutical inhibited tumor growth and induced apoptosis in vivo in breast cancer xenografts grown on the chick chorioallantoic membrane (CAM). Among eight different boswellic and lupeolic acids tested, β-ABA exhibited the highest cytotoxicity against MDA-MB-231 with an IC= 5.9µM, inhibited growth of cancer xenografts in vivo, and released proinflammatory cytokinesIts content in nutraceuticals correlated strongly with TNF-, IL-6, and IL-8 release inhibition.

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PMID: 

J Oleo Sci. 2019 ;68(10):1003-1009. PMID: 31582666

Abstract Title: 

The Effects of Frankincense Essential Oil on Stress in Rats.

Abstract: 

Frankincense essential oil, obtained from Boswellia carteri, is a popular essential oil, which is widely used in many parts of the world. While some of its properties are known, its effects on stress and sleep have not been studied. The effects of frankincense essential oil and its major components, limonene andα-pinene, on plasma corticosterone and glutathione (GSH) levels, as well as on sleep and wakefulness behaviour, were studied in sleep-deprived rats. The substances were applied topically after dilution in jojoba oil (vehicle). As compared to vehicle, frankincense essential oil at a dilution of 1/1000 (1:10) significantly reduced corticosterone levels (p

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PMID: 

J Food Biochem. 2019 Nov ;43(11):e12994. Epub 2019 Jul 28. PMID: 31659812

Abstract Title: 

Anti-inflammatory properties of fermented pine (Pinus morrisonicola Hay.) needle on lipopolysaccharide-induced inflammation in RAW 264.7 macrophage cells.

Abstract: 

This study was aimed to explore the antioxidant and anti-inflammatory activity of various pine needle products (non-fermented, fermented, and commercial) extracted with different solvents (hexane, ethyl acetate, and water) in lipopolysaccharide (LPS) induced RAW 264.7 cells. The phenolic/flavonoid contents of ethyl acetate extract of fermented pine needle (EAE-FPN) is higher than other pine product extracts (hexane/water). The levels of antioxidant indices (TEAC, DPPH) as well as free radical scavenging activity (HO) were significantly improved in EAE-FPN than other pine needle product extracts. The levels of ROS and various inflammatory markers (NO, PGE2, TNF-α, and IL-1β/6) were considerably abolished by EAE-FPN in a dose-dependent manner (50-200 μg/ml). Moreover, the protein expressions of inducible NO synthase (iNOS), cyclooxygenase 2 (COX-2), and nuclear factor Kappa B (NF-κB) p65 subunit were also markedly downregulated by EAE-FPN. Collectively, EAE-FPN with phenolic/flavonoid content showed excellent antioxidant and anti-inflammatory properties via modulating NF-κB signaling pathway. PRACTICAL APPLICATIONS: Pine needle drink (Pinus morrisonicola Hay) has been used as a functional beverage for many years due to its various biological properties in Asia especially in Taiwan, China, and Korea. Many researchers hinted various biological activity of fermented pine needle product but none of them explored the in-depth mechanism underpinning its antioxidant and anti-inflammatory properties in LPS-induced RAW 264.7 cell model. Hence, thecurrent cell line study was designed to assess the underlying mechanism behind the antioxidant and anti-inflammatory activity of Pine needles extract (both non-fermented and fermented) in LPS-induced RAW 264.7 cells (macrophage). The outcome of this study distinctly showed that EAE-FPN displayed potent antioxidant and anti-inflammatory activities by regulating NF-κB signaling pathway. Therefore, pine needle could be developed into functional drink to abolish the progression of inflammatory responses in various disease condition.

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PMID: 

J Neurol Neurosurg Psychiatry. 2018 04 ;89(4):330-338. Epub 2017 Dec 16. PMID: 29248894

Abstract Title: 

A standardised frankincense extract reduces disease activity in relapsing-remitting multiple sclerosis (the SABA phase IIa trial).

Abstract: 

OBJECTIVE: To investigate whether oral administration of a standardised frankincense extract (SFE) is safe and reduces disease activity in patients with relapsing-remitting multiple sclerosis (RRMS).METHODS: We performed an investigator-initiated, bicentric phase IIa, open-label, baseline-to-treatment pilot study with an oral SFE in patients with RRMS (NCT01450124). After a 4-month baseline observation phase, patients were treated for 8 months with an option to extend treatment for up to 36 months. The primary outcome measures were the number and volume of contrast-enhancing lesions (CEL) measured in MRI during the 4-month treatment period compared with the 4-month baseline period. Eighty patients were screened at two centres, 38 patients were included in the trial, 28 completed the 8-month treatment period and 18 of these participated in the extension period.RESULTS: The SFE significantly reduced the median number of monthly CELs from 1.00 (IQR 0.75-3.38) to 0.50 (IQR 0.00-1.13; difference -0.625, 95% CI -1.25 to -0.50; P

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PMID: 

J Transl Med. 2018 05 21 ;16(1):132. Epub 2018 May 21. PMID: 29784005

Abstract Title: 

CD8T cells mediate the antitumor activity of frankincense and myrrh in hepatocellular carcinoma.

Abstract: 

BACKGROUND: Tumor-promoting inflammation is an emerging hallmark of cancer, which participates in both cancer progression and immune escape. Hepatocellular carcinoma (HCC) is a typical inflammation-related cancer with an extremely poor prognosis. Frankincense and myrrh are anti-inflammation agents commonly used in clinic. The purpose of this study is to investigate whether extract of frankincense and myrrh (FM) downregulates inflammatory microenvironment of HCC and thereby restores antitumor immune responses.METHODS: The water-decocting FM was obtained and quantified. HCC cell lines HCCLM3 and Hepa1-6 were used to evaluate the efficacy of FM targeting NF-κB and STAT3 signaling with western blot and qRT-PCR analysis. CD8NKG2Dcells were derived from human peripheral blood and were used for evaluation of immune cells-mediated inflammation and oncolysis on HCCLM3 cells. The antitumor efficacy of FM was investigated both in immune compromised and immune competent mice bearing subcutaneous HCC. Mice received daily oral gavage of FM at 60 mg/kg. Immune activity within tumor microenvironment (TME) was assessed by ELISpot assay and flow cytometry, respectively. Depletion of CD8T cells or NK cells was achieved by intraperitoneal injection of respective neutralizing antibody.RESULTS: FM significantly inhibited the activation of NF-κB and STAT3 signaling in HCC cells induced by cytokines (TNF-α or IL-6) and in co-culture system with CD8NKG2Dcells. Furthermore, FM sensitized HCC cells to CD8NKG2Dcells-mediated oncolysis. In HCC-bearing mice, FM at a non-toxic dose failed to reduce tumor growth in immune compromised mice, whereas it significantly inhibited tumor growth and prolonged life span in immune competent mice. While the number of IFN-γ-producing cells within TME was increased in mice treated with FM, the infiltration of CD8T cells and NK cells was not increased. Finally, we identified that depletion of CD8T cells rather than NK cells abrogated the antitumor activity of FM.CONCLUSIONS: Our results show for the first time that CD8T cells mediate the antitumor activity of FM at a non-toxic dose. This may provide new insights to this ancient mysterious prescription in cancer therapy, which offers a novel and practical therapeutic strategy and the possibilities of combined immunotherapy for HCC as well as other inflammation-related cancers in clinic.

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PMID: 

Front Pharmacol. 2018 ;9:387. Epub 2018 Apr 20. PMID: 29731716

Abstract Title: 

Protective Effect of Casperome, an Orally Bioavailable Frankincense Extract, on Lipopolysaccharide- Induced Systemic Inflammation in Mice.

Abstract: 

Despite recent advances in critical care, sepsis remains a crucial cause of morbidity and mortality in intensive care units. Therefore, the identification of new therapeutic strategies is of great importance. Since ancient times, frankincense is used in traditional medicine for the treatment of chronic inflammatory disorders such as rheumatoid arthritis. Thus, the present study intends to evaluate if Casperome(Casp), an orally bioavailable soy lecithin-based formulation of standardized frankincense extract, is able to ameliorate systemic effects and organ damages induced by severe systemic inflammation using a murine model of sepsis, i.e., intraperitoneal administration of lipopolysaccharides (LPS).Male 60-day-old mice were assigned to six treatment groups: (1) control, (2) LPS, (3) soy lecithin (blank lecithin without frankincense extract), (4) Casp, (5) soy lecithin plus LPS, or (6) Casp plus LPS. Soy lecithin and Casp were given 3 h prior to LPS treatment; 24 h after LPS administration, animals were sacrificed and health status and serum cytokine levels were evaluated. Additionally, parameters representing liver damage or liver function and indicating oxidative stress in different organs were determined. Furthermore, markers for apoptosis and immune cell redistribution were assessed by immunohistochemistry in liver and spleen.LPS treatment caused a decrease in body temperature, blood glucose levels, liver glycogen content, and biotransformation capacity along with an increase in serum cytokine levels and oxidative stress in various organs. Additionally, apoptotic processes were increased in spleen besides a pronounced immune cell infiltration in both liver and spleen. Pretreatment with Casp significantly improved health status, blood glucose values, and body temperature of the animals, while serum levels of pro-inflammatory cytokines and oxidative stress in all organs tested were significantly diminished. Finally, apoptotic processes in spleen, liver glycogen loss, and immune cell infiltration in liver and spleen were distinctly reduced. Casp also appears to induce various cytochromeP450 isoforms, thus causing re-establishment of liver biotransformation capacity in LPS-treated mice.Casp displayed anti-inflammatory, anti-oxidative, and hepatoprotective effects. Thus, orally bioavailable frankincense extracts may serve as a new supportive treatment option in acute systemic inflammation and accompanied liver dysfunction.