The clinical efficacy of Olibanum gum chewing in patients with Mild-to-Moderate Alzheimer disease: A randomized Parallel-Design controlled trial.

BACKGROUND: Alzheimer's disease is a common neurodegenerative disorder in elderly with progressive decline in cognitive functions. This study aimed to investigate the possible memory-improving effects of Olibanum on patients with Alzheimer's disease. RESEARCH DESIGN AND METHOD: This double-blind, randomized clinical trial was carried out on 72 participants aged 50-75 years. The intervention group (n = 36) received 1.6 g/day of olibanum chewing gum for 18 weeks. The placebo group (n = 36) received chewing gum without olibanum. Neuropsychological assessments were performed at baseline, every 4 weeks, and after 18 weeks of the intervention. RESULTS: There was no significant difference between (MD: 0.84, 95%CI: -1.10 to 2.78, p = 0.392) at baseline. Both groups had linear improvements over time. There was no significant difference between two groups regarding the improvements after the intervention (F = 0.157, p = 0.693). There were no significant differences between the groups for MMSE score (Mini-Mental State Examination) after the intervention (F = 0.141, p = 0.708). CONCLUSIONS: This study revealed that 18 weeks of gum chewing with Olibanum did not change the neuropsychological status. More clinical studies are needed to confirm these findings.

Basis with RNA-Seq and WGCNA to explore the effect of Frankincense essential oil on dextran sodium sulfate-induced ulcerative colitis through MAPK/NF-κB signaling.

PURPOSE: Frankincense has been shown in studies to have healing benefits for people with ulcerative colitis (UC). However, its underlying mechanisms have not been fully investigated. The objective of this study was to explore the potential molecular mechanisms of Frankincense essential oil (FREO) in improving dextran sodium sulfate (DSS)-induced UC from multiple perspectives. METHODS: The FREO components were analyzed by GC-MS, and the interactions between the key active components and the mechanism of FREO were determined based on RNA-seq, "quantity-effect" weighting coefficient network pharmacology, WGCNA and pharmacodynamic experiments. The protection of FREO against DSS-induced UC mice was assessed by behavioral and pathological changes through mice. The expression of pro-inflammatory cytokines was measured using enzyme-linked immunosorbent assay. The expression of MAPK and NF-κB-related proteins by the Western Blotting and immunohistochemistry method. RESULTS: Treatment with FREO significantly improved the symptoms of weight loss, diarrhea, stool blood, and colon shortening in UC mice. Reduced intestinal mucosal damage and the degree of inflammatory cell infiltration in the colon. Decreased TNF-α and IL-6 levels in mice's serum and inhibited phosphorylation of ERK, p65 in MAPK and NF-κB signaling. CONCLUSION: FREO may decrease the inflammatory response to reduce the symptoms of UC by modulating the MAPK/ NF-κB pathway. This may be due to the synergistic interaction of the effective ingredient Hepten-2-yl tiglate, 6-methyl-5-, Isoneocembrene A and P-Cymene. This study provides a promising drug candidate and a new concept for the treatment of UC.

Targeted delivery of genistein for pancreatic cancer treatment using hyaluronic-coated cubosomes bioactivated with frankincense oil.

Pancreatic cancer is an aggressive malignancy that remains a major cause of cancer-related deaths. Research for innovative anticancer therapeutic options is thus imperative. In this regard, phytotherapeutics offer great promise as efficient treatment modalities, especially leveraging nanodrug delivery. Herein, we innovatively coloaded the flavonoid genistein (Gen) and frankincense essential oil (FO) within cubosomes, which were then coated with the bioactive ligand hyaluronic acid (HA/Gen-FO-Cub) for active-targeting of pancreatic cancer. The novel HA/Gen-FO-Cub displayed optimum nanosize (198.2 ± 4.5 nm), PDI (0.27 ± 0.01), zeta-potential (-34.7 ± 1.2 mV), Gen entrapment (99.3 ± 0.01 %), and controlled Gen release (43.7 ± 1.2 % after 120 h). HA/Gen-FO-Cub exerted selective anticancer activity on pancreatic cancer cells (PANC-1; 8-fold drop in IC50), cellular uptake and anti-migratory effect compared to Gen solution. HA/Gen-FO-Cub revealed prominent cytocompatibility (100 ± 5.9 % viability of human dermal fibroblast). Moreover, HA/Gen-FO-Cub boosted the in vivo anticancer activity of Gen in an orthotopic cancer model, affording tumor growth suppression (2.5-fold drop) and downregulation of NFκB and VEGF (2.9- and 1.8-fold decrease, respectively), compared to Gen suspension. Antimetastatic efficacy and Bcl-2-downexpression was histologically confirmed. Our findings demonstrate the promising anticancer aptitude of HA/Gen-FO-Cub as an effective phytotherapeutic nanodelivery system for pancreatic cancer therapy.

Preparation and characterization of brain-targeted polymeric nanocarriers (Frankincense-PMBN-lactoferrin) and in-vivo evaluation on an Alzheimer's disease-like rat model induced by scopolamine.

Experiments have demonstrated that frankincense may offer protection against scopolamine-induced Alzheimer's disease by mitigating cholinergic dysfunction and inhibiting inflammatory mediators. Nevertheless, its instability and limited water solubility lead to diminished medicinal efficacy. In this study, we utilized PMBN (poly [MPC-co-(BMA)-co-(MEONP)]) as a nanocarrier for targeted brain drug delivery of frankincense, employing lactoferrin as a ligand for precise targeting. Characterization of nanoparticle properties was conducted through FTIR and FESEM analysis, and the in-vitro drug release percentage from the nanoparticles was quantified. To induce Alzheimer's-like dementia in rats, scopolamine was intraperitoneally administered at a dose of 1 mg/kg/day for 14 days. Subsequently, behavioral assessments (Y-maze, passive avoidance test, tail suspension test) were performed, followed by evaluations of acetylcholinesterase (AChE), reduced glutathione (GSH), catalase (CAT), and brain histopathology at the conclusion of the treatment period. The results revealed that the nanoparticles had a size of 106.6 nm and a zeta potential of -3.8 mV. The maximum release of frankincense in the PBS environment from PMBN nanoparticles was 18.2 %, in accordance with the Peppas model. Behavioral tests indicated that targeted drug nanoparticles (F-PMBN-Lf) exhibited the capability to alleviate stress and depression while enhancing short-term memory in scopolamine-induced animals. Additionally, F-PMBN-Lf counteracted the scopolamine-induced elevation of AChE activity and GSH levels. However, it resulted in decreased activity of the antioxidant enzyme CAT compared to the scopolamine group. Histological analysis of brain tissue suggested that F-PMBN-Lf exerted a notable neuroprotective effect, preserving neuronal cells in contrast to the scopolamine-induced group. It appears that the polymer nanoparticles containing this plant extract have introduced a novel neuroprotective approach for the treatment of Alzheimer's disease.

Evaluation of the therapeutic effect of Olibanum extract against enteric and intramuscular phases of trichinosis in experimentally infected mice.

Trichinosis is a global food-borne zoonotic disease. Most drugs used in its treatment have low bioavailability and reduced activity against larvae. Therefore, there is an urgent need for safe and effective medications. This study aimed to investigate the in vivo anti-parasitic and anti-inflammatory efficacy of olibanum (OL) extract, alone or combined with albendazole (ABZ) during both intestinal and muscular phases of trichinosis. Male Swiss albino mice (n = 130) were allocated to seven groups, with 20 mice in each group except for the negative control group (10 mice): negative control (GI), positive control (GII), OL25- treated (GIII), OL50- treated (GIV), ABZ50- treated (GV), OL25 + ABZ25 (GVI), and OL50 + ABZ25 (GVII). For intestinal and muscular phase analysis, each group was divided into two subgroups based on euthanizing day (6 and 35 days post-infection). The drug's efficacy was evaluated through parasitological, biochemical, histopathological, and immunohistochemical studies. OL extract at both concentrations (25 mg/kg/d, 50 mg/kg/d) significantly reduced adult (53.7% and 68.1%, respectively) and larval counts (57.3% and 78.8%, respectively). It improved the histopathological changes in intestine and muscle. The expression of CD8+ T cells and the serum level of IL-10 increased significantly during both intestinal and muscular phases (P < 0.05) in OL50 treated mice. Additionally, OL decreased abnormal levels of liver enzymes (ALT & AST). Its effects were dose-dependent in both adult and larval stages. In conclusion, OL exhibits promising in vivo activity against both stages of Trichinella spiralis infection, particularly at the intramuscular phase. It can be safe as an alternative treatment for trichinosis.

Efficacy of frankincense-based herbal product in urinary incontinence: A randomized, double-blind, placebo- and active-controlled clinical trial.

Urinary incontinence is a silent epidemic that has a serious impact on a person's quality of life (QOL). This study aimed to evaluate the efficacy of frankincense-based herbal product (FHP) in urinary incontinence compared with placebo and solifenacin. In this randomized, double-blind clinical trial, 120 postmenopausal women with mixed urinary incontinence were randomized to one of the three groups of FHP, placebo, and standard treatment (solifenacin). Frequency, amount of leakage, and score of urinary incontinence as well as the QOL were measured at the end of the second and fourth weeks and 2 weeks after the interruption of the treatment. The ICIQ-UI SF and I-QOL questionnaires were used for the measurements. Mean frequency of urinary incontinence and amount of leakage significantly decreased in the FHP and solifenacin groups in the fourth week compared to the placebo group. In addition, 2 weeks after treatment completion, the effects of the FHP were significant compared to the solifenacin group. Due to the effect of FHP on improving the QOL and also the prolonged effect of this drug, the use of FHP in urinary incontinence, as a complementary treatment could be suggested.

Boswellic acids ameliorate neurodegeneration induced by AlCl3: the implication of Wnt/ß-catenin pathway.

Alzheimer's disease (AD) is a neurodegenerative disease (ND) that represents the principal cause of dementia. Effective treatment is still lacking. Without prevention, Alzheimer's disease (AD) incidence is expected to triple within 30 years. The risk increases in highly polluted areas and is positively linked to chronic aluminum (Al) exposure. Canonical Wingless-Int (Wnt)/ß-catenin pathway has been found to play a considerable role in ND pathogenesis. Resins of Boswellia serrata (frankincense) have been used traditionally for their psychoactive activity, in addition to their memory-boosting effects. Boswellic acids (BA) are pentacyclic triterpenes. They have antioxidant, anti-inflammatory, antinociceptive, and immunomodulatory activities. This study aimed to elucidate the role of the Wnt/ß-catenin pathway in BA protective activity against aluminum-induced Alzheimer's disease. For 6 weeks, rats were treated daily with AlCl3 (100 mg/kg/i.p.) either alone or with BA (125 or 250 mg/kg PO). Results indicated that BA significantly improved learning and memory impairments induced by AlCl3 treatment. Moreover, BA treatment significantly decreased acetylcholinesterase levels and reduced amyloid-beta (Aß) expression. In addition, BA ameliorated the increased expression of tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1ß), inhibited lipid peroxidation, and increased total antioxidants in the brain. Indeed, BA significantly suppressed AlCl3-induced decrease of brain-derived neurotrophic factor, pGSK-3ß (Ser 9), and ß-catenin. BA (250 mg/kg) showed a significant protective effect compared to a lower dose. The results conclude that BA administration modulated the expression of Wnt/ß-catenin pathway-related parameters, contributing to BA's role against Al-induced Alzheimer's disease. Effect of Boswellic acids on AlCl3-induced neurodegenerative changes. ChE cholinesterase, Ach acetylcholine, BDNF brain-derived neurotrophic factor, IL-1ß interleukin-1ß, TNF-α tumor necrosis factor-α.

Anti-inflammatory and anti-cancer activities of frankincense: Targets, treatments and toxicities.

The oleogum resins of Boswellia species known as frankincense have been used for ages in traditional medicine in India, China and the Arabian world independent of its use for cultural and religious rituals in Europe. During the past two decades, scientific investigations provided mounting evidence for the therapeutic potential of frankincense. We conducted a systematic review on the anti-inflammatory and anti-cancer activities of Boswellia species and their chemical ingredients (e.g. 3-O-acetyl-11-keto-ß boswellic acid, α- and ß-boswellic acids, 11-keto-ß-boswellic acid and other boswellic acids, lupeolic acids, incensole, cembrenes, triterpenediol, tirucallic acids, and olibanumols). Frankincense acts by multiple mechanisms, e.g. by the inhibition of leukotriene synthesis, of cyclooxygenase 1/2 and 5-lipoxygenase, of oxidative stress, and by regulation of immune cells from the innate and acquired immune systems. Furthermore, frankincense modulates signaling transduction responsible for cell cycle arrest and inhibition of proliferation, angiogenesis, invasion and metastasis. Clinical trials showed the efficacy of frankincense and its phytochemicals against osteoarthritis, multiple sclerosis, asthma, psoriasis and erythematous eczema, plaque-induced gingivitis and pain. Frankincense revealed beneficial effects towards brain tumor-related edema, but did not reduce glioma size. Even if there is no treatment effect on brain tumors itself, the management of glioma-associated edema may represent a desirable improvement. The therapeutic potential against other tumor types is still speculative. Experimental toxicology and clinical trials revealed only mild adverse side effects. More randomized clinical trials are required to estimate the full clinical potential of frankincense for cancer therapy.

Lipid Mediator Profiles Predict Response to Therapy with an Oral Frankincense Extract in Relapsing-Remitting Multiple Sclerosis.

Lipid mediators (LMs) are a unique class of immunoregulatory signalling molecules and known to be affected by frankincense extracts. We performed LM profiling by metabololipidomics in plasma samples from 28 relapsing-remitting multiple sclerosis (RR-MS) patients who took a standardised frankincense extract (SFE) daily for eight months in a clinical phase IIa trial (NCT01450124) and in 28 age- and gender-matched healthy controls. Magnetic resonance imaging, immunological outcomes and serum neurofilament light chain levels were correlated to changes in the LM profiles of the RR-MS cohort. Eight out of 44 analysed LMs were significantly reduced during an eight-month treatment period by the SFE and seven of these eight significant LM derive from the 5-lipoxygenase (5-LO) pathway. Baseline levels of 12- and 15-LO products were elevated in patients who exhibited disease activity (EDA) during SFE treatment compared to no-evidence-of-disease-activity (NEDA) patients and could predict treatment response to the SFE in a prediction model at baseline. Oral treatment with an SFE significantly reduces 5-LO-derived LMs in RR-MS patients during an eight-month treatment period. Treatment response to an SFE, however, seems to be related to 12-,15-LO and cyclooxygenase product levels before SFE exposure. Further studies should confirm their biomarker potential in RR-MS and SFE treatment.

The effect of frankincense (Boswellia serrata, oleoresin) and ginger (Zingiber officinale, rhizoma) on heavy menstrual bleeding: A randomized, placebo-controlled, clinical trial.

OBJECTIVES: To evaluate the effect of frankincense (Boswellia serrata, oleoresin) and ginger (Zingiber officinale, rhizoma) as complementary treatments for heavy menstrual bleeding (HMB) among women of reproductive age. DESIGN: Randomized, placebo-controlled, clinical trial. SETTING: Gynecology outpatient clinics. INTERVENTIONS: Patients with HMB (n = 102) were randomly assigned to three groups. All patients received ibuprofen (200 mg) and either frankincense (300 mg), ginger (300 mg), or a placebo, which contains 200 mg anhydrous lactose as the filling agent and was similar in appearance to the two other drugs. Patients received the medications three times a day for seven days of the menstrual cycle, starting from the first bleeding day and this was repeated for two consecutive menstrual cycles. MAIN OUTCOME MEASURES: Amount and duration of menstrual bleeding and quality of life (QOL). RESULTS: Duration of menstrual bleeding was decreased in the frankincense (-1.77 ± 2.47 days, P = 0.003) and ginger (-1.8 ± 1.79 days, P = 0.001) groups, but not in the placebo group (-0.52 ± 1.86 days, P = 0.42). Amount of menstrual bleeding was decreased in all (P < 0.05), with no difference among the study groups (P > 0.05). More improvement in QOL was observed in the frankincense (-25.7 ± 3.1; P < 0.001) and ginger (-29.2 ± 3.7: P < 0.001) groups compared to the placebo group (-15.07 ± 3.52; P < 0.001) and between the groups, differences were statistically significant (P = 0.02). CONCLUSIONS: Ginger and frankincense seem to be effective complementary treatments for HMB. Further studies with a larger sample size and longer follow-up are warranted in this regard.

Frankincense Essential Oil as a Supportive Therapy for Cancer-Related Fatigue: A Case Study.

Fatigue experienced by patients diagnosed with cancer can be debilitating and can be challenging to manage. The use of supportive therapies such as essential oils is gaining popularity among patients diagnosed with cancer. This article describes one patient's experience using frankincense (Boswellia carterii) essential oil to help in the management of her fatigue. The topical application of the frankincense helped to take her fatigue from being barely able to lift her head to being able to do some basic activities of daily living.

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

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<0.0001) at months 5-8. We observed significantly less brain atrophy as assessed by parenchymal brain volume change (P=0.0081). Adverse events were generally mild (57.7%) or moderate (38.6%) and comprised mainly gastrointestinal symptoms and minor infections. Mechanistic studies showed a significant increase in regulatory CD4+ T cell markers and a significant decrease in interleukin-17A-producing CD8+ T cells indicating a distinct mechanism of action of the study drug. INTERPRETATION: The oral SFE was safe, tolerated well and exhibited beneficial effects on RRMS disease activity warranting further investigation in a controlled phase IIb or III trial. CLINICAL TRIAL REGISTRATION: NCT01450124; Results.

Cancer Chemopreventive Effects of Boswellia sacra Gum Resin Hydrodistillates on Invasive Urothelial Cell Carcinoma: Report of a Case.

A 52-year-old Hispanic male presented with hematuria and was later diagnosed with a large invasive high-grade urothelial cell carcinoma (UCC) of the urinary bladder, but with ambiguous pT1/pT2 staging regarding musclaris propria invasion by UCC. The conventional treatment including radical cystoprostatectomy followed by neoadjuvant chemotherapy with or without radiation therapy was presented. The patient decided to delay the standard therapy until a later stage, but elected to go through transurethral resection of bladder tumor (TURBT) without Bacillus Calmette-Guérin instillation. Following TURBT, the patient started oral Boswellia sacra gum resin (aka frankincense or Ru Xiang in Chinese) hydrodistillates (BSGRH) administration at 3 mL daily with lifestyle changes, and continued this regimen in the last 25 months. Within the first year after diagnosis, the patient experienced 2 recurrences. Recurrent tumors were removed by TURBT alone and both tumors were far smaller than the original one. After the second recurrence, the patient has no detectible cancer in the bladder based on cystoscopy for 14 months and has an intact genitourinary system. His liver and kidney functions are considered to be normal based on blood chemistry tests. This index case suggests that BSGRH may have cancer chemopreventive effects on UCC. The use of Boswellia-derived products in the management of cancer has been well document in other published studies, and boswellic acids have been suggested to be the major component. However, BSGRH contains very little boswellic acids. Demonstration of cancer chemoprevention using BSGRH is one step forward in isolating the key components other than boswellic acids in frankincense. The critical question as to whether these components can simultaneously activate multiple pathways in cancer cells to execute cancer suppression/cytotoxicity or prevention effects remains to be addressed. More studies including identification of key molecules, pharmacokinetics of major compounds, as well as long-term benefits and possible adverse effects will be needed to meet the guidelines of the US Food and Drug Administration for botanical drug development.

Frankincense and myrrh suppress inflammation via regulation of the metabolic profiling and the MAPK signaling pathway.

Frankincense and myrrh are highly effective in treatment of inflammatory diseases, but lacking of thetherapy mechanisms. We undertook this study to evaluate the effects on Adjuvant-induced Arthritis(AIA) rats and to explore the underlying mechanisms by analyzing the metabolic profiling and signalingpathway evaluated by expression of inflammatory cytokines, c-jun and c-fos and corresponding phosphorylationlevels. [corrected]. The results stated the elevated expression levels of TNFα, PGE2, IL-2, NO, and MDA in serum and swelling paw of AIA rats were significantly decreased after treatment, which exerted more remarkable inhibitive effects of combined therapy. The metbolic profiling of plasma and urine were clearly improved and twenty-one potential biomarkers were identified. Moreover, the inhibited effects of five bioactive components on cytokine transcription in PHA stimulated-PBMC showed the MAPK pathway might account for this phenomenon with considerable reduction in phosphorylated forms of all the three MAPK (ERK1/2, p38 and JNK) and down regulation of c-jun and c-fos.