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Knee osteoarthritis (OA) has recently been ranked as the 11th highest contributor to global disability. More than 40% of patients use complementary and alternative medicine including supplements containing phytoextracts with anti-inflammatory properties as those from the Boswellia genus. The aim of this meta-analysis was to evaluate the efficacy of phytoextracts from the oleogum resin of the Boswellia genus as supplementation for patients affected by knee OA. Four electronic databases were used for the research and PRISMA statements were followed throughout the study. The following inclusion criteria were used: (a) the subjects of the study were humans with a diagnosis of knee OA reported by medical staff; (b) randomization and the presence of control (placebo, negative or positive control), and (c) outcomes reported with WOMAC and/or visual analog scale (VAS) score. Publication bias was assessed with a funnel plot and through the Egger test. The Jadad scale was used in order to assess the quality of the studies included. The statistical heterogeneity was assessed using I 2 statistics. Results of meta-analysis and subgroup analysis were reported using a forest plot. A total of 13 studies involving 850 (WOMAC) and 1185 (VAS) patients met the inclusion criteria. The meta-analysis did not detect a significant effect of the use of Boswellia extracts between the control and the treatment groups due to the high heterogeneity of the studies (p = 0.0865 for WOMAC) and (p = 0.3966 VAS). However, the subsequent subgroup analysis demonstrated the significant beneficial effect of Boswellia extracts in the treatment of knee OA with respect to a placebo (lower WOMAC score in the treatment groups). This was also confirmed in the meta-regression applied to the WOMAC scores. This is an important finding as people exposed to NSAID-related adverse effects could benefit from the use of Boswellia extracts. However, further high-quality studies are needed to establish the clinical efficacy of extracts from the genus Boswellia., (© 2024 The Author(s). Phytotherapy Research published by John Wiley & Sons Ltd.)

Background: Extracts from Boswellia serrata gum resin have anti-inflammatory effect and are used for treatment of a variety of chronic inflammatory diseases. It was previously demonstrated that the treatment with Boswellia serrata gum resin of LADA (Latent Autoimmune Diabetes in Adults) patients decreased blood levels of IA2 antibodies, one of the markers associated with LADA autoimmune diabetes., Primary Study Objective: The purpose of this study was to test whether Boswellia serrata gum resin also influences GAD65 autoantibodies as the other marker associated with LADA., Methods/design: We report a case study of male patient diagnosed with LADA with positive GAD65 autoantibodies who was treated with extract from Boswellia serrata gum resin, during 9 months. Blood levels of GAD65 autoantibodies, fasting blood glucose levels and HbA1c were measured before the treatment and periodically during the treatment., Results: Over the observed period, the blood levels of GAD65 autoantibodies linearly decreased about 25%., Conclusion: The study confirms that extract of Boswellia serrata gum resin seems to prevent insulitis in patients with LADA, as indicated by its action on both markers of autoimmune diabetes, i.e., GAD65 and IA2 autoantibodies. The possibility that the treatment with boswellic acids of LADA patients with positive autoantibodies could be beneficial on the course of the disease, calls for further investigation and a clinical study.

Ethnopharmacological Relevance: Semen Pharbitidis, the seeds of Pharbitis nil (Linn.) Choisy (Convolvulaceae) is a well-known traditional Chinese medicinal plant used for treating helminthiasis and epilepsy in China., Aim of the Study: This study aims to identify the anti-seizure components from Semen Pharbitidis., Methods: A bioassay-guided isolation of anti-seizure compounds from Semen Pharbitidis was performed using a zebrafish pentylenetetrazol seizure model. The structures of active compounds were elucidated by high resolution mass spectrometry. The fragments of active compounds were tested for anti-seizure activity as well., Results: The bioassay-guided isolation of ethanol extract of Semen Pharbitidis led to a group of resin glucosides, namely pharbitin. One of the fragments of pharbitin, 2-methylbutyric acid, also showed anti-seizure activity., Conclusions: We provided further experimental scientific evidence to support the traditional use of Semen Pharbitidis for the treatment of epilepsy. Pharbitin was identified to be the main anti-seizure component in Semen Pharbitidis., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Proven the great potential of essential oils as anticancer agents, the current study intended to explore molecular mechanisms responsible for in vitro and in vivo anti-colon cancer efficacy of essential oil containing oleo-gum resin extract (RH) of Mesua ferrea. MTT cell viability studies showed that RH had broad spectrum cytotoxic activities. However, it induced more profound growth inhibitory effects towards two human colon cancer cell lines i.e., HCT 116 and LIM1215 with an IC 50 values of 17.38 ± 0.92 and 18.86 ± 0.80 μg/mL respectively. RH induced relatively less toxicity in normal human colon fibroblasts i.e., CCD-18co. Cell death studies conducted, revealed that RH induced characteristic morphological and biochemical changes in HCT 116. At protein level it down-regulated expression of multiple pro-survival proteins i.e., survivin, xIAP, HSP27, HSP60 and HSP70 and up-regulated expression of ROS, caspase-3/7 and TRAIL-R2 in HCT 116. Furthermore, significant reduction in invasion, migration and colony formation potential was observed in HCT 116 treated with RH. Chemical characterization by GC-MS and HPLC methods revealed isoledene and elemene as one the major compounds. RH showed potent antitumor activity in xenograft model. Overall, these findings suggest that RH holds a promise to be further studied for cheap anti-colon cancer naturaceutical development., (Copyright © 2018 Elsevier Masson SAS. All rights reserved.)

Hypothesis/purpose: The aim of the present study was to evaluate in vivo the potential anti-ischemic and antiatheromatic activity of Chios Mastic gum, the resin of the trunk and branches of "Pistacia lentiscus var. chia", used since antiquity in traditional Greek medicine. The main compounds of mastic are triterpenes, possessing phytosterol-like structures. This led to the hypothesis that mastic and particularly its neutral fraction, enriched in phytosterol-like compounds, possess antiatheromatic activities., Methods: Total Mastic Extract without Polymer (TMEWP) and the neutral mastic fraction (NMF) were administered orally for 6 weeks to normal fed and to cholesterol fed rabbits in the form of sunflower oil solution. All the animals were randomly divided into 6 groups, anesthetized and subjected to 30min ischemia of the heart, followed by 3h reperfusion: At the end of the experiment the area at risk and the infarct zone were determined with the aid of fluorescent particles and triphenyl tetrazolium chloride staining, and small segments of the ascending and descending aorta and the heart were taken for histologic examination. Blood samples were collected at different time points of ischemia and reperfusion, for malondialdehyde (MDA) evaluation as an index of lipid peroxidation, for total and LDL cholesterol determination and for evaluation of oxidized LDL., Results: In the normal fed animals the NMF and the TMEWP reduced significantly the infarct size, while in the hypercholesterolemic rabbits both treatments were ineffective. Atherosclerosis was detected in all the animals fed cholesterol enriched diet in the form of subintimal accumulation of lipids and foamy macrophages. There was no detection of atherosclerosis in Groups treated with TMEWP and NMF, which both reduced the total cholesterol levels by 47 and 88% respectively, whilst had not effect on LDL oxidation. TMEWP and NMF reduced the MDA concentration in normal fed rabbits, but had no effect on MDA levels in cholesterol fed animals. TMEWP and NMPF reduce the infarct size in normal animals and possess significant antiatheromatic and hypolipidemic activities in rabbits fed cholesterol enriched diet., (Copyright © 2016 Elsevier GmbH. All rights reserved.)

For thousands of years, Chios Gum Mastic (CGM), the resin produced by the trunk of Pistachia lentiscus var Chia, has been used for culinary and medicinal purposes and several therapeutic properties have been attributed to it. CGM has been used in traditional medicine of various nations in the eastern Mediterranean area. This survey was carried out to identify biological mechanisms that could explain traditional usage and recent pharmacological findings. We reviewed the related scientific literature available from the NCBI PUBMED database on CGM studies and on natural products showing peroxisome proliferator-activated receptor (PPAR) agonist effects. We investigated whether CGM qualifies as a PPAR modulator. A large number of studies demonstrate that CGM has antioxidant, anti-inflammatory, hypolipidemic, and anticancer properties. Recently, the first evidence of CGM antidiabetic effect became known. CGM chemical composition has been extensively analyzed and the presence of several compounds, especially triterpenoids is well documented. Some of them, oleanonic acid, oleanolic acid, and gallic acid are considered to act as PPAR modulators. PPARs are nuclear receptors functioning as transcription factors and thereby controlling cellular functions at the level of gene expression. PPARs are involved in the pathways of significant diseases, such as metabolic syndrome, diabetes mellitus, dyslipidemia, inflammation, atheromatosis, and neoplasias, constituting a key target for pharmacological interventions. This article proposes that the synergistic action of some constituents of CGM on PPARs and more precisely on both PPARs isotypes-α and -γ, may be one of the major biological mechanisms via which CGM exerts its multiple effects.

Purpose: The purpose was to investigate Chios mastic gum (CMG) extract as an potential anti-tumor agent for oral squamous cell carcinoma in vitro., Methods: We designed a study to examine the effects of CMG extracts on growth of oral squamous cell carcinoma cell line, YD-10B and to determine whether the extracts could induce apoptosis through the activation of caspase-3, using the common chemotherapeutic agent Paclitaxel (Taxol, Bristol-Myers Squibb) as a control., Results: MTT assay suggested that both CMG and Taxol inhibited the proliferation of YD-10B cells in a time and dose dependent manner. Moreover, 10 μg/mL of CMG and 50 μg/mL of Taxol caused fragmentation of the genomic DNA at 24 hour. Finally, 10 μg/mL of CMG and 50 μg/mL of Taxol caused cleavage of procaspase-3 in western blot analysis., Conclusions: These results suggest CMG's potential as an anti-tumor agent.

Several Ferula (Umbelliferae) species have been used in Iranian traditional medicine as antiflatulent, antispasmodic, anticonvulsant, expectorant, etc. In the present study, cytotoxicity and anticonvulsant activity of the methanol extracts from several Ferula species were evaluated. Air-dried samples of different parts of these plants (Ferula diversivittata Regel & Schmalh. (roots), Ferula persica Willd. (aerial parts), Ferula ovina (Boiss.) Boiss. (roots), Ferula badrakema Kos.-Pol. (roots), Ferula diversivittata (flowers), Ferula latisecta Rech. F. & Aell. (roots), and Ferula badrakema (fruits)) were macerated with methanol for 3 days. The mixtures were then filtered, concentrated and dried. For determination of the cytotoxicity of the extracts and also the oleo-gum-resin of F. assafoetida L., the brine shrimp (Artemia salina) was employed as a model assay system since it provides a convenient in-house pre-screening method for evaluating general cytotoxicity. The methanol extracts of different Ferula species and the oleo-gum-resin of F. assafoetida exhibited cytotoxic effect with LC(50) values in the range of 6-321 microg/mL. For the anticonvulsant testing, seizure was induced by injection of pentylenetetrazole (PTZ), 90 mg/kg intraperitoneally (i.p.). This dose was given to 10 groups, each consisting of 6 mice, which were pretreated i.p. with the extracts (300 mg/kg), Diazepam (10 mL/kg) or saline (10 mL/kg). The results showed that none of the tested Ferula species can prevent PTZ-induced seizure at the used dose. In conclusion, all of the extracts and the oleo-gum resin of F. assafoetida showed dose-dependent cytotoxicity which was highest in F. badrakema fruits and lowest in F. badrakema roots. Our findings also revealed that the methanol extracts and F. assafoetida oleo-gum resin do not possess anticonvulsant activity.

Background: Guggul, herbal extract from resin of the Commiphora mukul tree, is widely used in Asia as a cholesterol-lowering agent based on Indian Ayurvedic medicine. Its popularity for this use is increasing in the US and Western Europe. Guggulsterones, the presumed bioactive compounds of guggul, may antagonise two nuclear hormone receptors involved in cholesterol metabolism, which is a possible explanation for hypolipidemic effects of these extracts. However, publications of efficacy data on the use of guggul extracts in Western populations are scarce., Objective: To study the efficacy of a guggul-based formulation (short: guggul) on blood lipids in healthy adults with moderately increased cholesterol., Methods: Double-blind, randomised, placebo controlled trial in Norwegian general practice. 43 women and men, age 27-70, with moderately increased cholesterol, randomised to use 2160mg guggul (4 capsules) daily, or placebo for 12 weeks., Outcome Measures: Mean change in total cholesterol, low-density lipoprotein cholesterol (LDL-C), triglycerides, high-density lipoprotein cholesterol (HDL-C) and total cholesterol/HDL-C ratio compared with baseline. Lipids were analysed at baseline, and at 6 and 12 weeks. In addition, unexpected events and adverse effects were recorded., Results: Two dropouts, one withdrawal, and incomplete lab results for six persons left 34 participants to accomplish the trial (18-guggul, 16-placebo) with complete lab test data. After 12 weeks, mean levels of total cholesterol and HDL-C in the active group were significantly reduced compared with the placebo group. However, the mean levels of LDL-C, triglycerides, and total cholesterol/HDL-C ratio between the two groups did not change significantly. Ten guggul users (vs. four in the placebo group) reported side effects: mild gastrointestinal discomfort (n=7), possible thyroid problems (n=2), and generalized skin rash (n=1). The latter resulted in withdrawal from trial., Conclusions: Even if total cholesterol and HDL-C were significantly reduced, the clinical magnitude of this remains obscure. More and larger studies are needed to establish effects and safety of guggul-based formulations in the treatment for hypercholesterolemia.

A hexane extract of the plant product Chios mastic gum (He-CMG) is demonstrated to kill human colon cancer cells in vitro via the process of anoikis. Specifically, the sequence of events includes He-CMG-induced GI-arrest of the cells, detachment of the cells from the substrate and subsequent apoptosis. Anoikis is dependent on the concentration and duration of treatment with He-CMG. Presence of the pan-caspase inhibitor, Z-VAD-fmk, did not prevent cell detachment, but it did prevent apoptosis of the detached cells indicating that the process of cell detachment, but not apoptosis, is independent of caspase activation. He-CMG-induced apoptosis is associated with activation of the initiator caspases-8, and -9 and the effector caspase-3. Caspases are activated in cells at a relatively long time after detachment, and caspase-3 activation may require caspase-8 or caspase-9 activation, as determined by using HCT116 isogenic clones impaired in apoptosis mechanisms that involve these two caspases. Finally, electron microscopy observations indicated a time-dependent appearance of morphological features both typical and non-typical of apoptosis in cells treated with He-CMG for various periods of time. Taken together, the results demonstrated that He-CMG induces apoptosis in HCT116 cells and, therefore, further in vivo and in vitro studies of the anticancer activities of this plant product are warranted.

Patients studied here suffered from chronic colitis characterized by vague lower abdominal pain, bleeding per rectum with diarrhoea and palpable tender descending and sigmoid colon. The inflammatory process in colitis is associated with increased formation of leukotrienes causing chemotaxis, chemokinesis, synthesis of superoxide radicals and release of lysosomal enzymes by phagocytes. The key enzyme for leukotriene biosynthesis is 5-lipoxygenase. Boswellic acids were found to be non-redox, non-competitive specific inhibitors of the enzyme 5-lipoxygenase. We studied the gum resin of Boswellia serrata for the treatment of this disease. Thirty patients, 17 males and 13 females in the age range of 18 to 48 years with chronic colitis were included in this study. Twenty patients were given a preparation of the gum resin of Boswellia serrata (900 mg daily divided in three doses for 6 weeks) and ten patients were given sulfasalazine (3 gm daily divided in three doses for 6 weeks) and served as controls. Out of 20 patients treated with Boswellia gum resin 18 patients showed an improvement in one or more of the parameters: including stool properties, histopathology as well as scanning electron microscopy, besides haemoglobin, serum iron, calcium, phosphorus, proteins, total leukocytes and eosinophils. In the control group 6 out of 10 patients showed similar results with the same parameters. Out of 20 patients treated with Boswellia gum resin 14 went into remission while in case of sulfasalazine remission rate was 4 out of 10. In conclusion, this study shows that a gum resin preparation from Boswellia serrata could be effective in the treatment of chronic colitis with minimal side effects.

The gum resin of Boswellia serrata, known in Indian Ayurvedic system of medicine as Salai guggal, contains boswellic acids, which have been shown to inhibit leukotriene biosynthesis. In a double-blind, placebo-controlled study forty patients, 23 males and 17 females in the age range of 18 - 75 years having mean duration of illness, bronchial asthma, of 9.58 +/- 6.07 years were treated with a preparation of gum resin of 300 mg thrice daily for a period of 6 weeks. 70% of patients showed improvement of disease as evident by disappearance of physical symptoms and signs such as dyspnoea, rhonchi, number of attacks, increase in FEV subset1, FVC and PEFR as well as decrease in eosinophilic count and ESR. In the control group of 40 patients 16 males and 24 females in the age range of 14-58 years with mean of 32.95 +/- 12.68 were treated with lactose 300 mg thrice daily for 6 weeks. Only 27% of patients in the control group showed improvement. The data show a definite role of gum resin of Boswellia serrata in the treatment of bronchial asthma.

Sterculia with and without a smooth-muscle relaxant (alverine citrate) had similar beneficial effects on constipation and reduced the transit times in diverticular disease. Intracolonic pressure, however, varied with the preparation used. Though both preparations relieved the symptoms of diverticular disease, the one containing alverine citrate was more effective. Part of the mode of action of bran may be to relax the smooth muscle of the gut, since its actions were more comparable to those of sterculia plus alverine citrate than to those of sterculia alone.

The effect of mastic, a concrete resinous exudate obtained from the stem of the tree Pistacia lentiscus, has been studied on experimentally-induced gastric and duodenal ulcers in rats. Mastic at an oral dose of 500 mg/kg produced a significant reduction in the intensity of gastric mucosal damage induced by pyloric ligation, aspirin, phenylbutazone, reserpine and restraint + cold stress. It produced a significant decrease of free acidity in 6-h pylorus-ligated rats and a marked cytoprotective effect against 50% ethanol in rats which could be reversed by prior treatment with indomethacin. The protective effect was not seen when it was given intraperitoneally in phenylbutazone and restraint + cold stress models. The reduction in the intensity of ulceration in cysteamine-induced duodenal ulcers was not found to be statistically significant in mastic-pretreated rats. The results suggest that mild antisecretory and a localized adaptive cytoprotectant action may be responsible for its anti-ulcer activity. These observations support the results of an earlier study on the clinical effectiveness of mastic in the therapy of duodenal ulcer.

A double-blind clinical trial was carried out on thirty-eight patients with symptomatic and endoscopically proven duodenal ulcer to compare the therapeutic responses to mastic (1 g daily, twenty patients) and placebo (lactose, 1 g daily, eighteen patients) given orally over a period of 2 weeks. Symptomatic relief was obtained in sixteen (80%) patients on mastic and in nine (50%) patients on placebo, while endoscopically proven healing occurred in fourteen (70%) patients on mastic and four (22%) patients on placebo. The differences between treatments were highly significant (P less than 0.01). Mastic was well tolerated and did not produce side effects. It is concluded that mastic has an ulcer healing effect, but further studies are needed to establish its role in treating peptic ulcer.