Extensive chromatographic isolation and purification of the extracts of the stem bark of Calophyllum inophyllum and Calophyllum soulattri have resulted in 11 xanthones. C. inophyllum gave inophinnin (1), inophinone (2), pyranojacareubin (5), rheediaxanthone A (6), macluraxanthone (7) and 4-hydroxyxanthone (8), while C. soulattri afforded soulattrin (3), phylattrin (4), caloxanthone C (9), brasixanthone B (10) and trapezifolixanthone (11). The structures of these compounds were determined on the basis of spectroscopic analyses such as 1D and 2D NMR, GC-MS, IR and UV. Cytotoxicity screening (MTT assay) carried out in vitro on all the xanthones using five human cancer cell lines indicated good activities for some of these xanthones. The structure-activity relationship study revealed that the inhibitory activities exhibited by these xanthone derivatives to be closely related to the existence and nature of the pyrano and the prenyl substituent groups on their skeleton.
A series of ninety-seven diarylpentanoid derivatives were synthesized and evaluated for their anti-inflammatory activity through NO suppression assay using interferone gamma (IFN-γ)/lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. Twelve compounds (9, 25, 28, 43, 63, 64, 81, 83, 84, 86, 88 and 97) exhibited greater or similar NO inhibitory activity in comparison with curcumin (14.7 ± 0.2 µM), notably compounds 88 and 97, which demonstrated the most significant NO suppression activity with IC50 values of 4.9 ± 0.3 µM and 9.6 ± 0.5 µM, respectively. A structure-activity relationship (SAR) study revealed that the presence of a hydroxyl group in both aromatic rings is critical for bioactivity of these molecules. With the exception of the polyphenolic derivatives, low electron density in ring-A and high electron density in ring-B are important for enhancing NO inhibition. Meanwhile, pharmacophore mapping showed that hydroxyl substituents at both meta- and para-positions of ring-B could be the marker for highly active diarylpentanoid derivatives.
A new coumarin, hoseimarin (1), together with four other xanthones, trapezifolizanthone (2), osajaxanthone (3), β-mangostin (4) and caloxanthone A (5), were isolated from the stem bark of Calophyllum hosei. The structures of these compounds were established by using spectroscopic analysis which included (1)H NMR, (13)C NMR, COSY, DEPT, HMQC and HMBC experiments.
A series of new pyrazoline derivatives (1b-4c) bearing N-acyl arms and nine to twelve carbon long alkoxy side chains was synthesized and characterized on the basis of spectroscopic data and microanalysis. The nature of self-assembly to understand the interplay of alkoxy chain crystallization and various supramolecular interactions was investigated using single crystal X-ray diffraction studies. Interesting self-assembled supramolecular structures of 1b and 4c were observed in the crystal lattice owing to various CH⋯O, H⋯H, CH⋯π, lonepair⋯π and π⋯π interactions. Further, all the synthesized compounds (1b-4c) were screened for their in vitro antifungal and anti-inflammatory activities. Compounds 2b, 3b, 2c and 3c showed significant to moderate antifungal activity against Microsporum canis whereas most of the other compounds were found inactive against all the five tested fungal strains. Good anti-inflammatory activity was observed for compounds 1b with IC50 value 331 μM compared to 273 μM for Indomethacine, a standard reference drug. The bio-activity data demonstrates the relationship between lipophilicity, solubility and bioavailability.
The clycoxygenase (COX) enzyme forms locally active prostaglandins responsible for producing inflammation and pain. Classical non-steroidal anti-inflammatory drugs (NSAID) inhibit the COX-2 enzyme that produces inflammatory prostaglandins as well as the COX-1 enzyme that produces gastric mucosa protecting prostaglandins. By specifically inhibiting only the COX-2 enzyme, coxibs thus reduce pain but do not damage the gastric mucosa. However, COX-2 at the vascular endothelium produces antithrombotic prostaglandins, and so by inhibiting COX-2 enzyme, the coxibs promote thrombosis. Rofecoxib and valdecoxib have been withdrawn because of the adverse cardiovascular events they induce. Amongst presently available coxibs cardiovascular risk is highest with enterocoxib and lowest with celecoxib. NSAIDS also increase cardiovascular events, the risk is highest with diclofenac and lowest with naproxen. Paracetamol and corticosteroids induce hypertension, while steroids also adversely affect the heart from metabolic change as well as fluid retention. Aspirin is an anti-thrombotic agent because of its ability to inhibit the COX-1 enzyme that produces the pro-aggregatory thromboxane. However, it increases gastrointestinal bleeding, can promote fluid retention and is nephrotoxic, all of which may lead to adverse cardiovascular outcomes. Patients at especially high risk of cardiovascular events from analgesic use include the elderly, and those with heart failure, hypertension, rheumatoid arthritis, chronic renal disease, chronic obstructive airway disease and previous myocardial infarction, cerebrovascular disease or peripheral vascular disease. Adverse cardiovascular events can occur within a week of initiation of analgesic treatment.
The anti-inflammatory activity of zerumbone (1), a natural cyclic sesquiterpene isolated from Zingiber zerumbet Smith was investigated using carrageenan-induced paw edema and cotton pellet-induced granuloma tissue formation test in mice. It was demonstrated that intraperitoneal administration of 1 at a dose of 5, 10, 50 and 100 mg/kg produced significant dose-dependent inhibition of paw edema induced by carrageenan. It was also demonstrated that 1 at similar doses significantly suppressed granulomatous tissue formation in cotton pellet-induced granuloma test.
A series of 46 curcumin related diarylpentanoid analogues were synthesized and evaluated for their anti-inflammatory, antioxidant and anti-tyrosinase activities. Among these compounds 2, 13 and 33 exhibited potent NO inhibitory effect on IFN-gamma/LPS-activated RAW 264.7 cells as compared to L-NAME and curcumin. However, these series of diarylpentanoid analogues were not significantly inhibiting NO scavenging, total radical scavenging and tyrosinase enzyme activities. The results revealed that the biological activity of these diarylpentanoid analogues is most likely due to their action mainly upon inflammatory mediator, inducible nitric oxide synthase (iNOS). The present results showed that compounds 2, 13 and 33 might serve as a useful starting point for the design of improved anti-inflammatory agents.
Clausena excavata is a well-known plant used in folkloric medicine for the treatment of different ailments. This study aimed to determine the in vitro cytoxicity of its leaf solvent extracts as well as the in vivo wound healing and antioxidant activities of the methanolic extracts of C. excavata (MECE). HaCaT (keratocyte) and Vero cell lines were used for evaluation of the in vitro cytotoxic effects, while the in vivo wound healing and antioxidant activities were determined in skin wounds inflicted on rats. Twenty adult male Sprague-Dawley rats were divided into five groups of four animals each. Approximately 3.14 cm(2) excisional wound was inflicted on the nape of each rat following anesthesia. The treatment groups received topical application of MECE at 50 mg/mL (MECE-LD [low dose]), 100 mg/mL (MECE-MD [medium dose]), and 200 mg/mL (MECE-HD [high dose]), while the negative control group was treated with gum acacia in normal saline and the positive control group with intrasite gel. Wound contraction was evaluated on days 5, 10, and 15 after wound infliction, and tissue from wound area was collected at day 15 post-wound infliction for antioxidant enzyme evaluation and histopathological analyses. Generally, Vero cells were more resistant to the cytotoxic effects of the solvent extracts as compared with HaCaT cells. Chloroform (CH) and ethyl acetate (EA) extracts of C. excavata were toxic to HaCaT cells at 200 and 400 µg/mL, but the same concentrations showed higher (P<0.05) viability in Vero cells. There was significantly (P<0.01) greater wound contraction at days 10 and 15 post-wound infliction in all the treatment groups than in the control groups. Histopathologically, the MECE-HD-treated wound showed significantly (P<0.05) lesser inflammatory cell proliferation, degeneration, and distribution of granulation tissue than other groups. Similarly, the degree of collagen maturation, angiogenesis, and collagen distribution were significantly (P<0.05) lower in MECE-HD than in other groups. The MECE-HD, MECE-MD, and intrasite treatment groups showed a significantly (P<0.05) higher number of VEGF-positive and TGF-β1-positive cells in the skin wound than the control groups. The activities of superoxide dismutase and catalase were significantly (P<0.01) higher in the MECE-HD and intrasite treatment groups than in the other groups. Lipid peroxidase activity of the treated groups was significantly (P<0.01) lower than that in the control group. The study showed that MECE is a potent wound healing agent through anti-inflammatory and antioxidant effects that enhanced the rate of wound contraction, re-epithelialization, and collagen deposition. The effect of MECE is suggested to be due to its high polyphenolic compound content.
We determined the consumption of non-steroidal anti-inflammatory drugs (NSAIDs) and the prevalence of chronic renal impairment and renal papillary necrosis (RPN) in patients with various types of arthritis. Ninety-four patients with chronic arthritis who had consumed more than 1000 capsules and/or tablets of NSAIDs were studied. Renal profiles and radiological investigations such as intravenous urogram (IVU), ultrasonography (US) and computed tomography (CT) were performed to look for evidence of RPN. Twelve patients did not complete the study. Ten of the 82 patients who had completed the study (12.2%) had radiologic evidence of RPN. Five out of 53 patients (9.4%) with rheumatoid arthritis, three out of 11 patients (27.3%) with gouty arthritis and two out of seven patients (28.6%) with osteoarthritis had RPN. Renal impairment (serum creatinine levels of 125-451 mumol/l) was found in 20 patients (24.4%). The patients had consumed 1000-26,300 capsules and/or tablets over a period ranging from 1 yr to more than 30 yr. Patients with chronic arthritis who consume excessive amount of NSAIDs are at risk of developing RPN and chronic renal impairment.
1. This study examines the effect of Hoe 140, a bradykinin (BK) 2 receptor antagonist, indomethacin and prednisolone on chronic adjuvant arthritis of the knee in rats. We also evaluated the influence of Hoe 140 on BK-forming enzymes in the synovial and paw tissues. 2. Adjuvant arthritis was induced in male Sprague-Dawley rats in the right knee by injecting 0.05 ml of a fine suspension of heat-killed Mycobacterium tubercle bacilli in liquid paraffin (5 mg/ml). 3. Hoe 140 (1.5 mg/kg i.p.), indomethacin (2.5 mg/kg orally) and prednisolone (3.0 mg/kg orally) administration for 9 days resulted in significant suppression of knee joint swelling. Plasma and tissue kallikrein levels were raised (P < 0.01) in the synovial and paw tissues of adjuvant arthritic rats. Hoe 140 treatment reduced (P < 0.05) tissue kallikrein but increased (P < 0.01) plasma kallikrein levels in synovial tissue. 4. Hoe 140 treatment did not alter (P > 0.05) the raised plasma and tissue kallikrein levels in the paw tissue. The findings indicate that Hoe 140 may be a useful anti-inflammatory agent and BK plays a major role in this adjuvant-induced arthritis model.
Introduction: Benzimidazole analogues are bicyclic compounds that had been synthesized comprising the fusion of benzene and imidazole. It gains interest in research as it poses numerous therapeutic potential such as anti-ulcer, anti-malarial, anti-helminthic, anti-fungal, anti-inflammatory, and anti-cancer. Hence, this work aims to screen novel benzimidazole analogues using MTT assay for potential anti-proliferation activities on gastric cancer, which is the second cause of cancer-related death. Methods: MTT assay was conducted following standard protocol on HGT-1 gastric cancer cells. Cells were seeded and allowed to attach overnight before being introduced with various con-centration of benzimidazole analogues up to 72 hours and the optical density of the MTT was recorded using 560 nm wavelength. Two-Way ANOVA was used to analyse all data, followed by post-hoc Tukey test and the structure analysis relationship was analysed using MTT result. Results: From five analogues, only compound 4 showed an-ti-proliferation activity with IC50 8.212 ± 0.813 μM at 72 hours. Compound 4 had hydroxyl group at ortho- and para- position and remarkably, compound 2 which contained the hydroxyl group at ortho- and meta- position together with compound 5 which contained the combination of meta- and para- induced proliferation on gastric cancer. Conclusion: Different position of hydroxyl group on the benzene ring gives different activities on gastric cancer and from the experiment, only compound 4 had the anti-proliferative activity.
Ginkgolide A is a highly active platelet activating factor antagonist cage molecule which was isolated from the leaves of the Ginkgo biloba L. It is known for its inflammatory and immunological potentials. This review aims to sketch a current scenario on its therapeutic activities on the basis of scientific reports in the databases. A total 30 articles included in this review suggests that ginkgolide A has many important biological activities, including anti-inflammatory, anticancer, anxiolytic-like, anti-atherosclerosis and anti-atherombosis, neuro- and hepatoprotective effects. There is a lack of its toxicological (e.g. toxicity, cytotoxicity, genotoxicity and mutagenitcity) profile. In conclusion, ginkgolide A may be one of the potential therapeutic lead compounds, especially for the treatment of cardiovascular, hepatological, and neurological diseases and disorders. More studies are necessary on this hopeful therapeutic agent.
Thymoquinone (TQ) is the major active compound in black seed oil (BSO). Many pharmacological effects of TQ, such as anti-inflammatory, hypoglycemic, antioxidant, immune stimulator, and anticancer, have been reported. TQ can be considered as a biomarker for BSO, but its content in the commercial products is rarely reported. TQ content varies based on the oil source and extraction method. This study aimed to quantify the TQ content in the commercial BSO products in Malaysia and to evaluate whether the products can be used as a source of TQ for therapeutic benefits. TQ was quantified using an established high-performance liquid chromatography (HPLC) method. TQ human equivalent dose (HED) was calculated based on reported animal studies from literature, and theoretical BSO amount containing the TQ dose was calculated based on the HPLC analysis. TQ content in the commercial BSO products ranged from 0.07% wt/wt to 1.88% wt/wt. The product with the highest TQ concentration is approximately 27-fold higher than the product with the lowest TQ concentration. Consequently, theoretical BSO amounts needed for specific diseases varied and some products cannot provide practical amount of TQ. This study recommends the regulation of TQ content in BSO and suggests that the BSO might be fortified with extra TQ to be effectively used in some diseases.
1. Andrographis paniculata (Burm. f) Nees, commonly known as 'king of bitters', is a herbaceous plant belonging to the Family Acanthaceae. It has been widely used for centuries in Asian countries like China, India, Thailand and Malaysia for the treatment of sore throat, flu and upper respiratory tract infections. 2. Andrographolide, 14-deoxy-11,12-didehydroandrographolide and neoandrographolide are examples of the major labdane diterpenoids isolated from A. paniculata. These bioactive molecules have exhibited varying degrees of anti-inflammatory and anticancer activities in both in vitro and in vivo experimental models of inflammation and cancer. 3. Extensive libraries of andrographolide analogues have been synthesised mainly by modifying the α,β-unsaturated γ-butyrolactone moiety, the two double bonds Δ(8,(17)) and Δ(12,(13)) and the three hydroxyls at C-3 (secondary), C-14 (allylic) and C-19 (primary). Many of these synthetic analogues exhibit superior anticancer activity over the naturally occurring andrographolides. 4. Andrographolide and its derivatives have been shown to have anti-inflammatory effects in experimental models of asthma, stroke and arthritis, as well as in patients with upper respiratory tract infections. Andrographolide reduces the production of cytokines, chemokines, adhesion molecules, nitric oxide and lipid mediators, probably via inhibition of the nuclear factor (NF)-κB signalling pathway. 5. The anticancer mechanisms for andrographolide include inhibition of Janus tyrosine kinases-signal transducers and activators of transcription, phosphatidylinositol 3-kinase and NF-κB signalling pathways, suppression of heat shock protein 90, cyclins and cyclin-dependent kinases, metalloproteinases and growth factors, and the induction of tumour suppressor proteins p53 and p21, leading to inhibition of cancer cell proliferation, survival, metastasis and angiogenesis. 6. Andrographolide drug discovery is a promising strategy for the development of a novel class of anti-inflammatory and anticancer drugs.
Carotenoids are a diverse group of lipid-soluble pigments that exhibit potent biological activities such as antioxidant, anti-inflammatory, and provitamin A activities. The potent health benefits of carotenoids result in the surge in the market demands for carotenoids, especially natural carotenoids from sustainable sources. Microbial carotenoids have attracted considerable interests for many industrial applications because of the low costs and ease of scaling-up with shorter production time. There is a growing interest in the search of new and sustainable microbial sources and cost-efficient production strategies following the high economical values and vast commercial applications of carotenoids. This article presents a review on the industrial production strategies of microbial carotenoids from microalgae, fungi, and bacteria sources. The industrial significance of the mass production of microbial carotenoids is also discussed. The structure, classification, and biosynthesis pathway of the carotenoids are also presented in this review.
Viola betonicifolia (Violaceae) is commonly recognized as "Banafsha" and widely distributed throughout the globe. This plant is of great interest because of its traditional, pharmacological uses. This review mainly emphases on morphology, nutritional composition, and several therapeutic uses, along with pharmacological properties of different parts of this multipurpose plant. Different vegetative parts of this plant (roots, leaves, petioles, and flowers) contained a good profile of essential micro- and macronutrients and are rich source of fat, protein, carbohydrates, and vitamin C. The plant is well known for its pharmacological properties, e.g., antioxidant, antihelminthic, antidepressant, anti-inflammatory, analgesic, and has been reported in the treatment of various neurological diseases. This plant is of high economic value. The plant has potential role in cosmetic industry. This review suggests that V. betonicifolia is a promising source of pharmaceutical agents. This plant is also of significance as ornamental plant, however further studies needed to explore its phytoconstituents and their pharmacological potential. Furthermore, clinical studies are needed to use this plant for benefits of human beings.
Our aim was to compare the protective efficacy of two different formulations of methylprednisolone in T-2 toxin-induced cardiomyopathy. Methylprednisolone (soluble form, Lemod-solu® and/or depot form, Lemod-depo®, a total single dose of 40 mg/kg im) was given immediately after T-2 toxin (1 LD50 0.23 mg/kg sc). The myocardial tissue samples were examinated by using histopathology, semiquantitative and imaging analyses on day 1, 7, 14, 21, 28 and 60 of the study. Therapeutic application of Lemod-solu® significantly decreased the intensity of myocardial degeneration and haemorrhages, distribution of glycogen granules in the endo- and perimysium, a total number of mast cells and the degree of their degranulation was in correlation with the reversible heart structural lesions (p anti-inflammatory activity.
Curcumin is a small organic molecule with pleiotropic biological activities. However, its multiple structural-pharmacokinetic challenges prevent its development into a clinical drug. Various structural modifications have been made to improve its drug profile. In this review, we focus on the methods adopted in the synthesis of asymmetric curcumin derivatives and their biological activities and forecast the future of this exciting class of compounds in the field of medicine.
The effects of different drying methods, including sun-, oven-, and freeze-drying on the changes in the antioxidant and anti-inflammatory activities of ginger (Zingiber officinale var. Rubra) rhizome were studied. Sun-, oven-, and freeze-dried ginger showed a significant (p < 0.05) increase in phenolic content by 1.79, 1.53, and 1.91-fold; flavonoid content increased by 6.06, 5.27, and 4.90-fold; FRAP increased by 3.95, 3.51, and 3.15-fold; ABTS•+ scavenging activity increased by 2.07, 1.72, and 1.61-fold; and DPPH• inhibition increased by 78%, 58%, and 56%, respectively. Dried ginger also exhibited better inhibitory effects on the lipopolysaccharides-induced nitric oxide production in murine macrophage RAW 264.7. The drying process demonstrated a positive effect on the bioactivities of ginger. The sun-dried ginger exhibited the most potent antioxidant properties with the best enhanced anti-inflammatory activity followed by the oven-dried ginger and lastly, the freeze-dried ginger.
Among the symptoms of COVID-19 fever, general malaise, pain and aches, myalgia, fatigue, and headache can affect the quality of life of patients, even after the end of the acute phase of the infection and can be long lasting. The current treatment of these symptoms, also because COVID-19 patients have been asked not to use non-steroidal anti-inflammatory drugs (NSAIDs), in particular ibuprofen are often unsatisfactory. Among the above mentioned symptoms malaise and fatigue seem the most difficult to treat. In this case report we describe the use of kratom (Mitragyna speciosa) by a patient with confirmed COVID-19 infection. What we observed was a fast and sustained relieve of the above mentioned symptoms.