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Journal: BMC complementary and alternative medicine


BACKGROUND: Regardless of the availability of therapeutic options, the overall 5-year survival for patients diagnosed with pancreatic cancer remains less than 5%. Gum resins from Boswellia species, also known as frankincense, have been used as a major ingredient in Ayurvedic and Chinese medicine to treat a variety of health-related conditions. Both frankincense chemical extracts and essential oil prepared from Boswellia species gum resins exhibit anti-neoplastic activity, and have been investigated as potential anti-cancer agents. The goals of this study are to identify optimal condition for preparing frankincense essential oil that possesses potent anti-tumor activity, and to evaluate the activity in both cultured human pancreatic cancer cells and a xenograft mouse cancer model. METHODS: Boswellia sacra gum resins were hydrodistilled at 78 [degree sign]C; and essential oil distillate fractions were collected at different durations (Fraction I at 0–2 h, Fraction II at 8–10 h, and Fraction III at 11–12 h). Hydrodistillation of the second half of gum resins was performed at 100 [degree sign]C; and distillate was collected at 11–12 h (Fraction IV). Chemical compositions were identified by gas chromatography–mass spectrometry (GC-MS); and total boswellic acids contents were quantified by high-performance liquid chromatography (HPLC). Frankincense essential oil-modulated pancreatic tumor cell viability and cytotoxicity were determined by colorimetric assays. Levels of apoptotic markers, signaling molecules, and cell cycle regulators expression were characterized by Western blot analysis. A heterotopic (subcutaneous) human pancreatic cancer xenograft nude mouse model was used to evaluate anti-tumor capability of Fraction IV frankincense essential oil in vivo. Frankincense essential oil-induced tumor cytostatic and cytotoxic activities in animals were assessed by immunohistochemistry. RESULTS: Longer duration and higher temperature hydrodistillation produced more abundant high molecular weight compounds, including boswellic acids, in frankincense essential oil fraactions. Human pancreatic cancer cells were sensitive to Fractions III and IV (containing higher molecular weight compounds) treatment with suppressed cell viability and increased cell death. Essential oil activated the caspase-dependent apoptotic pathway, induced a rapid and transient activation of Akt and Erk1/2, and suppressed levels of cyclin D1 cdk4 expression in cultured pancreatic cancer cells. In addition, Boswellia sacra essential oil Fraction IV exhibited anti-proliferative and pro-apoptotic activities against pancreatic tumors in the heterotopic xenograft mouse model. CONCLUSION: All fractions of frankincense essential oil from Boswellia sacra are capable of suppressing viability and inducing apoptosis of a panel of human pancreatic cancer cell lines. Potency of essential oil-suppressed tumor cell viability may be associated with the greater abundance of high molecular weight compounds in Fractions III and IV. Although chemical component(s) responsible for tumor cell cytotoxicity remains undefined, crude essential oil prepared from hydrodistillation of Boswellia sacra gum resins might be a useful alternative therapeutic agent for treating patients with pancreatic adenocarcinoma, an aggressive cancer with poor prognosis.

Concepts: Cancer, Oncology, Apoptosis, Chemotherapy, Tumor, Neoplasm, Cell cycle, Pancreatic cancer


BACKGROUND: In ancient times, plants were recognized for their medicinal properties. Later, the arrival of synthetic drugs pushed it to the backstage. However, from being merely used for food, plants are now been widely explored for their therapeutic value. The current study explores the potential of skin and flesh extracts from a hard-necked Rocambole variety of purple garlic in preventing cardiomyocyte hypertrophy and cell death. METHODS: Norepinephrine (NE) was used to induce hypertrophy in adult rat cardiomyocytes pretreated with garlic skin and flesh extracts. Cell death was measured as ratio of rod to round shaped cardiomyocytes. Fluorescent probes were used to measure apoptosis and oxidative stress in cardiomyocytes treated with and without extracts and NE. Pharmacological blockade of nitric oxide (NO) and hydrogen sulfide (H2S) were used to elucidate the mechanism of action of garlic extracts. Garlic extract samples were also tested for alliin and allicin concentrations. RESULTS: Exposure of cardiomyocytes to NE induced an increase in cell size and cell death; this increase was significantly prevented upon treatment with garlic skin and flesh extracts. Norepinephrine increased apoptosis and oxidative stress in cardiomyocytes which was prevented upon pretreatment with skin and flesh extracts; NO, and H2S blockers significantly inhibited this beneficial effect. Allicin and alliin concentration were significantly higher in garlic flesh extract when compared to the skin extract. CONCLUSION: These results suggest that both skin and flesh garlic extracts are effective in preventing NE induced cardiomyocyte hypertrophy and cell death. Reduction in oxidative stress may also play an important role in the anti-hypertrophic and anti-apoptotic properties of garlic extracts. These beneficial effects may in part be mediated by NO and H2S.

Concepts: Nitrogen, Radical, Zinc, Sulfur, Garlic, Hydrogen sulfide, PReVENT, Allicin


Magnolia grandiflora L. flower is wildly used in Asian as a traditional herbal medication. The purpose of the study was to investigate the antimelanogenic and antioxidant properties of Magnolia grandiflora L. flower extract. In the study, the inhibitory effects of M. grandiflora L. flower extract on mushroom tyrosinase, B16F10 intracellular tyrosinase activity and melanin content were determined spectrophotometrically. Meanwhile, the antioxidative capacity of the flower extract was also investigated.

Concepts: Antioxidant, Melanin, Herbalism, Melanocyte, Tyrosinase, Magnolia, Magnolia grandiflora


Drugs dedicated to alleviate neurodegenerative diseases like Parkinson’s and Alzheimer’s have always been associated with debilitating side effects. Medicinal mushrooms which harness neuropharmacological compounds offer a potential possibility for protection against such diseases. Pleurotus giganteus (formerly known as Panus giganteus) has been consumed by the indigenous people in Peninsular Malaysia for many years. Domestication of this wild mushroom is gaining popularity but to our knowledge, medicinal properties reported for this culinary mushroom are minimal.

Concepts: Neurology, Neurodegenerative disorders, Latin America, Malaysia, Agaricus bisporus, Indigenous peoples, Agaricales, Pleurotus nebrodensis


BACKGROUND: Thuja orientalis has been traditionally used to treat patients who suffer from baldness and hair loss in East Asia. The present study sought to investigate the hair growth-promoting activity of T. orientalis hot water extract and the underlying mechanism of action. METHODS: After T. orientalis extract was topically applied to the shaved dorsal skin of telogenic C57BL/6 N mice, the histomorphometric analysis was employed to study induction of the hair follicle cycle. To determine the effect of T. orientalis extract on the telogen to anagen transition, the protein expression levels of beta-catenin and Sonic hedgehog (Shh) in hair follicles were determined by immunohistochemistry. RESULTS: We observed that T. orientalis extract promoted hair growth by inducing the anagen phase in telogenic C57BL/6 N mice. Specifically, the histomorphometric analysis data indicates that topical application of T. orientalis extract induced an earlier anagen phase and prolonged the mature anagen phase, in contrast to either the control or 1% minoxidil-treated group. We also observed increases in both the number and size of hair follicles of the T. orientalis extract-treated group. Moreover, the immunohistochemical analysis reveals earlier induction of beta-catenin and Shh proteins in hair follicles of the T. orientalis extract-treated group, compared to the control or 1% minoxidil-treated group. CONCLUSION: These results suggest that T. orientalis extract promotes hair growth by inducing the anagen phase in resting hair follicles and might therefore be a potential hair growth-promoting agent.

Concepts: Chemotherapy, Skin, Immunohistochemistry, Topical, Hair, Hair follicle, Sonic hedgehog, Sebaceous gland


BACKGROUND: Tinnitus, the perception of sound in absence of an external acoustic source, impairs the quality of life in 2% of the population. Since in most cases causal treatment is not possible, the majority of therapeutic attempts aim at developing and strengthening individual coping and habituation strategies. Therapeutic interventions that incorporate training in mindfulness meditation have become increasingly popular in the treatment of stress-related disorders. Here we conducted a randomized, controlled clinical study to investigate the efficacy of a specific mindfulness- and body-psychotherapy based program in patients suffering from chronic tinnitus. METHODS: Thirty-six patients were enrolled in this pilot study. The treatment was specifically developed for tinnitus patients and is based on mindfulness and body psychotherapy. Treatment was performed as group therapy at two training weekends that were separated by an interval of 7 weeks (eleven hours/weekend) and in four further two-hour sessions (week 2, 9, 18 and 22). Patients were randomized to receive treatment either immediately or after waiting time, which served as a control condition. The primary study outcome was the change in tinnitus complaints as measured by the German Version of the Tinnitus Questionnaire (TQ). RESULTS: ANOVA testing for the primary outcome showed a significant interaction effect time by group (F = 7.4; df = 1,33; p = 0.010). Post hoc t-tests indicated an amelioration of TQ scores from baseline to week 9 in both groups (intervention group: t = 6.2; df = 17; p < 0.001; control group: t = 2.5; df = 16; p = 0.023), but the intervention group improved more than the control group. Groups differed at week 7 and 9, but not at week 24 as far as the TQ score was concerned. CONCLUSIONS: Our results suggest that this mindfulness- and body-psychotherapy-based approach is feasible in the treatment of tinnitus and merits further evaluation in clinical studies with larger sample sizes.The study is registered with (NCT01540357).

Concepts: Experimental design, Clinical trial, Effectiveness,, Clinical research, Psychotherapy, Meditation, Mindfulness


BACKGROUND: Estrogen has been reported to accelerate cutaneous wound healing. This research studies the effect of young coconut juice (YCJ), presumably containing estrogen-like substances, on cutaneous wound healing in ovairectomized rats. METHODS: Four groups of female rats (6 in each group) were included in this study. These included sham-operated, ovariectomized (ovx), ovx receiving estradiol benzoate (EB) injections intraperitoneally, and ovx receiving YCJ orally. Two equidistant 1-cm full-thickness skin incisional wounds were made two weeks after ovariectomy. The rats were sacrificed at the end of the third and the fourth week of the study, and their serum estradiol (E2) level was measured by chemiluminescent immunoassay. The skin was excised and examined in histological sections stained with H&E, and immunostained using anti-estrogen receptor (ER-alpha an ER-beta) antibodies. RESULTS: Wound healing was accelerated in ovx rats receiving YCJ, as compared to controls. This was associated with significantly higher density of immunostaining for ER-alpha an ER-beta in keratinocytes, fibroblasts, white blood cells, fat cells, sebaceous gland, skeletal muscles, and hair shafts and follicles. This was also associated with thicker epidermis and dermis, but with thinner hypodermis. In addition, the number and size of immunoreactive hair follicles for both ER-alpha and ER-beta were the highest in the ovx+YCJ group, as compared to the ovx+EB group. CONCLUSIONS: This study demonstrates that YCJ has estrogen-like characteristics, which in turn seem to have beneficial effects on cutaneous wound healing.

Concepts: Wound healing, Healing, Estradiol, Skin, Dermis, Epidermis, Sebaceous gland, Coconut water


BACKGROUND: This study evaluated, using in vitro assays, the antibacterial, antioxidant, and tyrosinase-inhibition activities of methanolic extracts from peels of seven commercially grown pomegranate cultivars. METHODS: Antibacterial activity was tested on Gram-positive (Bacillus subtilis and Staphylococcus aureus) and Gram-negative bacteria (Escherichia coli and Klebsiella pneumonia) using a microdilution method. Several potential antioxidant activities, including radical-scavenging ability (RSA), ferrous ion chelating (FIC) and ferric ion reducing antioxidant power (FRAP), were evaluated. Tyrosinase enzyme inhibition was investigated against monophenolase (tyrosine) and diphenolase (DOPA), with arbutin and kojic acid as positive controls. Furthermore, phenolic contents including total flavonoid content (TFC), gallotannin content (GTC) and total anthocyanin content (TAC) were determined using colourimetric methods. HPLC-ESI/MSn analysis of phenolic composition of methanolic extracts was also performed. RESULTS: Methanolic peel extracts showed strong broad-spectrum activity against Gram-positive and Gram-negative bacteria, with the minimum inhibitory concentrations (MIC) ranging from 0.2 to 0.78 mg/ml. At the highest concentration tested (1000 mug/ml), radical scavenging activities were significantly higher in Arakta (83.54%), Ganesh (83.56%), and Ruby (83.34%) cultivars (P< 0.05). Dose dependent FIC and FRAP activities were exhibited by all the peel extracts. All extracts also exhibited high inhibition (>50%) against monophenolase and diphenolase activities at the highest screening concentration. The most active peel extract was the Bhagwa cultivar against monophenolase and the Arakta cultivar against diphenolase with IC50 values of 3.66 mug/ml and 15.88 mug/ml, respectively. High amounts of phenolic compounds were found in peel extracts with the highest and lowest total phenolic contents of 295.5 (Ganesh) and 179.3 mg/g dry extract (Molla de Elche), respectively. Catechin, epicatechin, ellagic acid and gallic acid were found in all cultivars, of which ellagic acid was the most abundant comprising of more than 50% of total phenolic compounds detected in each cultivar. CONCLUSIONS: The present study showed that the tested pomegranate peels exhibited strong antibacterial, antioxidant and tyrosinase-inhibition activities. These results suggest that pomegranate fruit peel could be exploited as a potential source of natural antimicrobial and antioxidant agents as well as tyrosinase inhibitors.

Concepts: Bacteria, Microbiology, Escherichia coli, Fruit, Tannin, Gram-negative bacteria, Pomegranate, Ferric


BACKGROUND: Stroke is one of the leading causes of death and disability in China. Current treatments for stroke are limited and achieve no optimal effect. Acupuncture is widely used in the treatment of stroke and in improving the quality of life for patients in China. In most previous clinical studies, the effects of acupuncture have been diverse, and few well-designed randomized controlled trials have been conducted to investigate the long-term effect of acupuncture on acute stroke recovery. METHOD: Three hundred and twenty eight subjects with acute cerebral apoplexy will be recruited. The patients will be randomized into two different groups: the intervention group will receive acupuncture treatment together with Western standard treatment for 2 weeks plus the secondary prevention treatment for 22 weeks; the control group will receive only the Western standard treatment for 2 weeks and the secondary prevention treatment for 22 weeks. The primary outcome measures are Barthel Index and the Stroke-Specific Quality Of Life. The secondary outcome measures are the National Institutes of Health Stroke Scale and Modified Rankin Scale. All assessments will be conducted at the baseline and at weeks 4, 12 and 24 of follow-up. DISCUSSION: This study will evaluate the effects of acupuncture on the long-term recovery of acute stroke and on improving the quality of life of the patients. The results of this study will help establish optimal integrated therapeutic strategies for patients with stroke.Trial registrationCurrent Controlled Trials ISRCTN29932220.

Concepts: Clinical trial, Randomized controlled trial, Effectiveness, Modified Rankin Scale, Pharmaceutical industry, Clinical research, Barthel scale, Rehabilitation medicine


BACKGROUND: The aim of this study was to screen various solvent extracts of whole plant of Torilis leptophylla to display potent antioxidant activity in vitro and in vivo, total phenolic and flavonoid contents in order to find possible sources for future novel antioxidants in food and pharmaceutical formulations. MATERIAL AND METHODS: A detailed study was performed on the antioxidant activity of the methanol extract of whole plant of Torilis leptophylla (TLM) and its derived fractions {n-hexane (TLH), chloroform (TLC) ethyl acetate (TLE) n-butanol (TLB) and residual aqueous fraction (TLA)} by in vitro chemical analyses and carbon tetrachloride (CCl4) induced hepatic injuries (lipid peroxidation and glutathione contents) in male Sprague-Dawley rat. The total yield, total phenolic (TPC) and total flavonoid contents (TFC) of all the fractions were also determined. TLM was also subjected to preliminary phytochemical screening test for various constituents. RESULTS: The total phenolic contents (TPC) (121.9+/-3.1 mg GAE/g extract) of TLM while total flavonoid contents (TFC) of TLE (60.9 +/-2.2 mg RTE/g extract) were found significantly higher as compared to other solvent fractions. Phytochemical screening of TLM revealed the presence of alkaloids, anthraquinones, cardiac glycosides, coumarins, flavonoids, saponins, phlobatannins, tannins and terpenoids. The EC50 values based on the DPPH (41.0+/-1 mug/ml), ABTS (10.0+/-0.9 mug/ml) and phosphomolybdate (10.7+/-2 mug/ml) for TLB, hydroxyl radicals (8.0+/-1 mug/ml) for TLC, superoxide radicals (57.0+/-0.3 mug/ml) for TLM and hydrogen peroxide radicals (68.0+/-2 mug/ml) for TLE were generally lower showing potential antioxidant properties. A significant but marginal positive correlation was found between TPC and EC50 values for DPPH, hydroxyl, phosphomolybdate and ABTS, whereas another weak and positive correlation was determined between TFC and EC50 values for superoxide anion and hydroxyl radicals. Results of in vivo experiment revealed that administration of CCl4 caused a significant increase in lipid peroxidation (TBARS) while decrease in GSH contents of liver. In contrast, TLM (200 mg/kg bw) and silymarin (50 mg/kg bw) co-treatment effectively prevented these alterations and maintained the antioxidant status. CONCLUSION: Data from present results revealed that Torilis leptophylla act as an antioxidant agent due to its free radical scavenging and cytoprotective activity.

Concepts: Oxygen, Antioxidant, Reactive oxygen species, Flavonoid, Chloroform, Methane, Hydroxyl radical, Lipid peroxidation