Herbal remedies in the management of hyperuricemia and gout: A review of in vitro, in vivo and clinical evidences.

Gout, or hyperuricemia is a multifactorial and multi-faceted metabolic disease that is quite difficult to manage and/or treat. Conventional therapies such as non-steroidal anti-inflammatory drugs (NSAIDs) such as allopurinol, corticosteroids and colchicine amongst others, have helped in its management and treatment to some extent. This study aimed to compile and analyze the different herbal remedies used in the management of hyperuricemia and gout. A literature search was conducted from key databases (PubMed, ScienceDirect, Cochrane Library, Google Scholar) using relevant keywords via the PRISMA model. Smilax riparia A.DC. from Traditional Chinese Medicine is used in many countries for its therapeutic effect on lowering serum urate levels. No single study was able to establish the efficacy of a specific traditionally used herb via in vitro, in vivo, and clinical studies. Patients were found to use a panoply of natural remedies, mainly plants to treat hyperuricemia and gout, which have been validated to some extent by in vitro, in vivo, and clinical studies. Nonetheless, further research is needed to better understand the ethnopharmacological relationship of such herbal remedies.

Exploring the pathophysiological influence of heme oxygenase-1 on neuroinflammation and depression: A study of phytotherapeutic-based modulation.

BACKGROUND: The heme oxygenase (HO) system plays a significant role in neuroprotection and reduction of neuroinflammation and neurodegeneration. The system, via isoforms HO-1 and HO-2, regulates cellular redox balance. HO-1, an antioxidant defense enzyme, is highlighted due to its association with depression, characterized by heightened neuroinflammation and impaired oxidative stress responses. METHODOLOGY: We observed the pathophysiology of HO-1 and phytochemicals as its modulator. We explored Science Direct, Scopus, and PubMed for a comprehensive literature review. Bibliometric and temporal trend analysis were done using VOSviewer. RESULTS: Several phytochemicals can potentially alleviate neuroinflammation and oxidative stress-induced depressive symptoms. These effects result from inhibiting the MAPK and NK-κB pathways - both implicated in the overproduction of pro-inflammatory factors - and from the upregulation of HO-1 expression mediated by Nrf2. Bibliometric and temporal trend analysis further validates these associations. CONCLUSION: In summary, our findings suggest that antidepressant agents can mitigate neuroinflammation and depressive disorder pathogenesis via the upregulation of HO-1 expression. These agents suppress pro-inflammatory mediators and depressive-like symptoms, demonstrating that HO-1 plays a significant role in the neuroinflammatory process and the development of depression.

Nanoparticles for Thrombus Diagnosis and Therapy: Emerging Trends in Thrombus-theranostics.

Cardiovascular disease is one of the chief factors that cause ischemic stroke, myocardial infarction, and venous thromboembolism. The elements that speed up thrombosis include nutritional consumption, physical activity, and oxidative stress. Even though the precise etiology and pathophysiology remain difficult topics that primarily rely on traditional medicine. The diagnosis and management of thrombosis are being developed using discrete non-invasive and non-surgical approaches. One of the emerging promising approach is ultrasound and photoacoustic imaging. The advancement of nanomedicines offers concentrated therapy and diagnosis, imparting efficacy and fewer side effects which is more significant than conventional medicine. This study addresses the potential of nanomedicines as theranostic agents for the treatment of thrombosis. In this article, we describe the factors that lead to thrombosis and its consequences, as well as summarize the findings of studies on thrombus formation in preclinical and clinical models and also provide insights on nanoparticles for thrombus imaging and therapy.

Phytoimmunomodulators: A review of natural modulators for complex immune system.

In the past few decades, the medicinal properties of plants and their effects on the human immune system are being studied extensively. Plants are an incredible source of traditional medicines that help cure various diseases, including altered immune mechanisms and are economical and benign compared to allopathic medicines. Reported data in written documents such as Traditional Chinese medicine, Indian Ayurvedic medicine support the supplementation of botanicals for immune defense reactions in the body and can lead to safe and effective immunity responses. Additionally, some botanicals are well-identified as magical herbal remedies because they act upon the pathogen directly and help boost the immunity of the host. Chemical compounds, also known as phytochemicals, obtained from these botanicals looked promising due to their effects on the human immune system by modulating the lymphocytes which subsequently reduce the chances of getting infected. This paper summarises most documented phytochemicals and how they act on the immune system, their properties and possible mechanisms, screening conventions, formulation guidelines, comparison with synthetic immunity-enhancers, marketed immunity-boosting products, and immune-booster role in the ongoing ghastly corona virus wave. However, it focuses mainly on plant metabolites as immunomodulators. In addition, it also sheds light on the current advancements and future possibilities in this field. From this thorough study, it can be stated that the plant-based secondary metabolites contribute significantly to immunity building and could prove to be valuable medicaments for the design and development of novel immunomodulators even for a pandemic like COVID-19.

Improvement in the Phytochemical Content and Biological Properties of Stevia rebaudiana (Bertoni) Bertoni Plant Using Endophytic Fungi Fusarium fujikuroi.

This study aimed to increase the therapeutic potential of medicinal plants through inoculation with endophytic fungi. As endophytes influence medicinal plants' biological properties, twenty fungal strains were isolated from the medicinal plant Ocimum tenuiflorum. Among all fungal isolates, the R2 strain showed the highest antagonistic activity towards plant pathogenic fungi Rosellinia necatrix and Fusarium oxysporum. The partial ITS region of the R2 strain was deposited in the GenBank nucleotide sequence databases under accession number ON652311 as Fusarium fujikuroi isolate R2 OS. To ascertain the impact of an endophytic fungus on the biological functions of medicinal plants, Stevia rebaudiana seeds were inoculated with Fusarium fujikuroi (ON652311). In the DPPH assay, the IC50 value of the inoculated Stevia plant extracts (methanol, chloroform, and positive control) was 72.082 µg/mL, 85.78 µg/mL, and 18.86 µg/mL, respectively. In the FRAP assay, the IC50 value of the inoculated Stevia extracts (methanol, chloroform extract, and positive control) was 97.064 µM Fe2+ equivalents, 117.662 µM Fe2+ equivalents, and 53.384 µM Fe2+ equivalents, respectively. In the extracts of the plant inoculated with endophytic fungus, rutin and syringic acid (polyphenols) concentrations were 20.8793 mg/L and 5.4389 mg/L, respectively, which were higher than in the control plant extracts. This approach can be further utilized for other medicinal plants to increase their phytochemical content and hence medicinal potential in a sustainable way.

Unveiling the Pharmacological and Nanotechnological Facets of Daidzein: Present State-of-the-Art and Future Perspectives.

Herbal drugs have been attracting much scientific interest in the last few decades and nowadays, phytoconstituents-based research is in progress to disclose their unidentified medicinal potential. Daidzein (DAI) is the natural phytoestrogen isoflavone derived primarily from leguminous plants, such as the soybean and mung bean, and its IUPAC name is 4',7-dihydroxyisoflavone. This compound has received great attention as a fascinating pharmacophore with remarkable potential for the therapeutic management of several diseases. Certain pharmacokinetic properties of DAI such as less aqueous solubility, low permeability, and poor bioavailability are major obstacles restricting the therapeutic applications. In this review, distinctive physicochemical characteristics and pharmacokinetics of DAI has been elucidated. The pharmacological applications in treatment of several disorders like oxidative stress, cancer, obesity, cardiovascular, neuroprotective, diabetes, ovariectomy, anxiety, and inflammation with their mechanism of action are explained. Furthermore, this review article comprehensively focuses to provide up-to-date information about nanotechnology-based formulations which have been investigated for DAI in preceding years which includes polymeric nanoparticles, solid lipid nanoparticles, nanostructured lipid carrier, polymer-lipid nanoparticles, nanocomplexes, polymeric micelles, nanoemulsion, nanosuspension, liposomes, and self-microemulsifying drug delivery systems.

The sub-acute toxicity of kavalactone in rats: a study of the effect of oral doses and the mechanism of toxicity in combination with ethanol.

Kava is a herbal supplement and beverage made from the Piper methysticum plant, which is known for its recreational use as a mood enhancer, relaxation, as well as pain relief for centuries. Kava is widely used among alcoholics, but it is dangerous and potentially fatal. The objectives of this study were to examine the sub-acute toxicity effects of different doses of 70% kavalactone (KL) in rats by oral application, as well as to elucidate the mechanisms of toxicity alone and in combination with ethanol (EtOH). The most common side effects observed were abnormal breathing, ataxia, lethargy, loss of appetite, indigestion, and loss of coordination, especially in the 800 mg/kg bw, po bodyweight dosage of kava treatment group alone, and in combination with EtOH. In the sub-acute study, there were dose-related decreases in body weight, feed intake, and water consumption rates. Gross and histopathological findings revealed that the liver was abnormal in color, size, consistency, and the weight significantly increased at a dose of 800 mg/kg bw, po, with KL alone and a greater increase in combination with EtOH. Hepatocellular hypertrophy (HP) and necrosis with Kupffer cells hyperplasia were observed in the periacinar zone of all rats dosed with KL (800 mg/kg bw, po) alone, and extensive changes were observed in combination with EtOH. The periportal (Z1) and mid-zonal (Z2) areas of hepatocytes were less affected as compared to the periacinar zone. These results demonstrate that EtOH exacerbated the sedative and hypnotic activity of KL, and markedly increased toxicity. The histopathological results supported the clinical and biochemical findings and the severity of hepatic damage in a dose-dependent manner.

Phytoconstituents Assisted Biofabrication of Copper Oxide Nanoparticles and Their Antiplasmodial, and Antilarval Efficacy: A Novel Approach for the Control of Parasites.

The present work aimed to biofabricate copper oxide nanoparticles (CuO NPs) using Tinospora cordifolia leaf extract. The biofabricated CuO NPs were treated against the malarial parasite of chloroquine-resistant Plasmodium falciparum (INDO) and the antilarval efficacy was evaluated against the malaria vector Anopheles stephensi and dengue vector Aedes aegypti. The prominence at 285 nm in the UV-visible spectrum helped to identify the produced CuO NPs. Based on the XRD patterns, the concentric rings correspond to reflections at 38.26° (111), 44.11° (200), 64.58° (220), and 77.34° (311). These separations are indicative of CuO's face-centered cubic (fcc) structure. The synthesized CuO NPs have FTIR spectra with band intensities of 3427, 2925, 1629, 1387, 1096, and 600 cm-1. The absorbance band at 3427 cm-1 is known to be associated with the stretching O-H due to the alcoholic group. FTIR proved that the presence of the -OH group is responsible for reducing and capping agents in the synthesis of nanoparticles (NPs). The synthesized CuO NPs were found to be polymorphic (oval, elongated, and roughly spherical) in form with a size range of 11-47 nm and an average size of 16 nm when the morphology was examined using FESEM and HRTEM. The highest antiplasmodial efficacy against the chloroquine-resistant strain of P. falciparum (INDO) was found in the synthesized CuO NPs, with LC50 values of 19.82 µg/mL, whilst HEK293 cells are the least toxic, with a CC50 value of 265.85 µg/mL, leading to a selectivity index of 13.41. However, the antiplasmodial activity of T. cordifolia leaf extract (TCLE) and copper sulfate (CS) solution showed moderate activity, with LC50 values of 52.24 and 63.88 µg/mL, respectively. The green synthesized NPs demonstrated extremely high antilarval efficacy against the larvae of An. stephensi and Ae. aegypti, with LC50 values of 4.06 and 3.69 mg/L, respectively.

Targeting Nanotechnology and Nutraceuticals in Obesity: An Updated Approach.

HYPOTHESIS: This review article represents a brief layout of the risk factors and pathophysiology responsible for obesity, customary treatment strategies, and nanotechnology-based nutraceutical for the therapeutics of obesity. EXPERIMENTS: An exhaustive search of the literature was done for this purpose, using Google Scholar, PubMed, and ScienceDirect databases. A literature study was conducted using publications published in peer-reviewed journals between 2000 and 2022. FINDINGS: This was revealed that risk factors responsible for obesity were genetic abnormalities and environmental and socio-economic factors. Several research articles published between 2000 and 2022 were based on phytoconstituents-based nanoformulation for obesity therapeutics and, therefore, have been systematically compiled in this review. Various nutraceuticals like Garcinia cambogia, quercetin, resveratrol, capsaicin, Capsicum, Curcuma longa, Camella Sinensis, Zingiber officinalis, Citrus aurantium, Aegle marmelos, Coffea canephora, Asparagus officinalis, Gardenia jasminoides, Catha edulis, Clusia nemroisa, Rosmarinus officinalis, Cirsium setidens, Betula platyphylla, Tripterygium wilfordi possessing anti-obesity actions are discussed in this review along with their patents, clinical trials as well as their nanoformulation available. CONCLUSION: This review illustrates that nanotechnology has a great propensity to impart a promising role in delivering phytochemicals and nutraceuticals in managing obesity conditions and other related disorders.

Pathogenesis and management of traumatic brain injury (TBI): role of neuroinflammation and anti-inflammatory drugs.

Traumatic brain injury (TBI) is an important global health concern that represents a leading cause of death and disability. It occurs due to direct impact or hit on the head caused by factors such as motor vehicles, crushes, and assaults. During the past decade, an abundance of new evidence highlighted the importance of inflammation in the secondary damage response that contributes to neurodegenerative and neurological deficits after TBI. It results in disruption of the blood-brain barrier (BBB) and initiates the release of macrophages, neutrophils, and lymphocytes at the injury site. A growing number of researchers have discovered various signalling pathways associated with the initiation and progression of inflammation. Targeting different signalling pathways (NF-κB, JAK/STAT, MAPKs, PI3K/Akt/mTOR, GSK-3, Nrf2, RhoGTPase, TGF-ß1, and NLRP3) helps in the development of novel anti-inflammatory drugs in the management of TBI. Several synthetic and herbal drugs with both anti-inflammatory and neuroprotective potential showed effective results. This review summarizes different signalling pathways, associated pathologies, inflammatory mediators, pharmacological potential, current status, and challenges with anti-inflammatory drugs.

Gastroprotective effect of low dose Eugenol in experimental rats against ethanol induced toxicity: Involvement of antiinflammatory and antioxidant mechanism.

ETHNOPHARMACOLOGICAL RELEVANCE: Syzygium aromaticum L. volatile oil (clove oil) has been traditionally used for various stomach disorders including inflammatory conditions. Eugenol is the major constituent present in the volatile oil, and it has been established as a gastroprotective agent through many published studies, but the exact and complete mechanism of ulcer protection is not delineated yet. Moreover, it plays precisely the opposite effect in higher dose in antiulcer properties with worsening the ulcer at a higher dose. AIM: This study aims to carry out the prophylactic cytoprotective effect of eugenol with single low doses and explore the probable interrelated underlying transcriptional and translational level mechanism of cytoprotection such as antioxidative, anti-inflammatory, mucous generation in rats using ethanol-induced ulcer model. METHODS: Rats were administered with different doses of eugenol before ethanol intragastrically. The effects of the eugenol on mucous production, Nitric oxide generation, PGE2 synthesis, lipid peroxidation were recorded together with cytokines measurement in the blood. TNF-α and IL-6, two key cytokines, were also studied in specific. In addition, studies on the immunohistochemical and gene expression of HSP70 and iNOS indicators have been conducted. RESULTS: According to our findings, Eugenol substantially reduced the ulcer index and completely protected the mucosa from lesions. By restoring the lowered GSH and NP-SH levels, the protective effect of the eugenol was found to be augmented at both doses. This finding has corresponded to an increase in MDA, which was lowered by ethanol administration. Pre-treatment with eugenol on the ethanol-induced ulcer reduced the plasma NO levels and increased PGE2 along with a decreased TNF-α and IL-6 concentration. Additionally, significant transcriptional and translational upregulation of HSP70 and downregulation of iNOS were detected in the eugenol-treated rat stomach tissue. CONCLUSION: Our findings demonstrated that eugenol had a considerable gastroprotective impact at low doses, which could be attributed to its ability to regulate inflammatory reactions and antioxidant capacity.

Medicinal Plants and Isolated Molecules Demonstrating Immunomodulation Activity as Potential Alternative Therapies for Viral Diseases Including COVID-19.

Plants have been extensively studied since ancient times and numerous important chemical constituents with tremendous therapeutic potential are identified. Attacks of microorganisms including viruses and bacteria can be counteracted with an efficient immune system and therefore, stimulation of body's defense mechanism against infections has been proven to be an effective approach. Polysaccharides, terpenoids, flavonoids, alkaloids, glycosides, and lactones are the important phytochemicals, reported to be primarily responsible for immunomodulation activity of the plants. These phytochemicals may act as lead molecules for the development of safe and effective immunomodulators as potential remedies for the prevention and cure of viral diseases. Natural products are known to primarily modulate the immune system in nonspecific ways. A number of plant-based principles have been identified and isolated with potential immunomodulation activity which justify their use in traditional folklore medicine and can form the basis of further specified research. The aim of the current review is to describe and highlight the immunomodulation potential of certain plants along with their bioactive chemical constituents. Relevant literatures of recent years were searched from commonly employed scientific databases on the basis of their ethnopharmacological use. Most of the plants displaying considerable immunomodulation activity are summarized along with their possible mechanisms. These discussions shall hopefully elicit the attention of researchers and encourage further studies on these plant-based immunomodulation products as potential therapy for the management of infectious diseases, including viral ones such as COVID-19.

An updated knowledge of Black seed (Nigella sativa Linn.): Review of phytochemical constituents and pharmacological properties.

N. sativa (N. sativa) has been used since ancient times, when a scientific concept about the use of medicinal plants for the treatment of human illnesses and alleviation of their sufferings was yet to be developed. It has a strong religious significance as it is mentioned in the religious books of Islam and Christianity. In addition to its historical and religious significance, it is also mentioned in ancient medicine. It is widely used in traditional systems of medicine for a number of diseases including asthma, fever, bronchitis, cough, chest congestion, dizziness, paralysis, chronic headache, back pain and inflammation. The importance of this plant led the scientific community to carry out extensive phytochemical and biological investigations on N. sativa. Pharmacological studies on N. sativa have confirmed its antidiabetic, antitussive, anticancer, antioxidant, hepatoprotective, neuro-protective, gastroprotective, immunomodulator, analgesic, antimicrobial, anti-inflammatory, spasmolytic, and bronchodilator activity. The present review is an effort to explore the reported chemical composition and pharmacological activity of this plant. It will help as a reference for scientists, researchers, and other health professionals who are working with this plant and who need up to date knowledge about it.

Bioactive Natural Antivirals: An Updated Review of the Available Plants and Isolated Molecules.

Viral infections and associated diseases are responsible for a substantial number of mortality and public health problems around the world. Each year, infectious diseases kill 3.5 million people worldwide. The current pandemic caused by COVID-19 has become the greatest health hazard to people in their lifetime. There are many antiviral drugs and vaccines available against viruses, but they have many disadvantages, too. There are numerous side effects for conventional drugs, and active mutation also creates drug resistance against various viruses. This has led scientists to search herbs as a source for the discovery of more efficient new antivirals. According to the World Health Organization (WHO), 65% of the world population is in the practice of using plants and herbs as part of treatment modality. Additionally, plants have an advantage in drug discovery based on their long-term use by humans, and a reduced toxicity and abundance of bioactive compounds can be expected as a result. In this review, we have highlighted the important viruses, their drug targets, and their replication cycle. We provide in-depth and insightful information about the most favorable plant extracts and their derived phytochemicals against viral targets. Our major conclusion is that plant extracts and their isolated pure compounds are essential sources for the current viral infections and useful for future challenges.

Antileukemic Effect of Palladium Nanoparticles Mediated by White Tea (Camellia sinensis) Extract In Vitro and in WEHI-3B-Induced Leukemia In Vivo.

This study investigated the in vivo antileukemic activity of palladium nanoparticles (Pd@W.tea-NPs) mediated by white tea extract in a murine model. The cell viability effect of Pd@W.tea-NPs, "blank" Pd nanoparticles, and white tea extract alone was determined in murine leukemia WEHI-3B cells and normal mouse fibroblasts (3T3 cells). Apoptotic and cell cycle arrest effects of Pd@W.tea-NPs in WEHI-3B cells were evaluated. The effects of Pd@W.tea-NPs administered orally to leukemic mice at 50 and 100 mg/kg daily over 28 days were evaluated. Pd@W.tea-NPs reduced the viability of WHEI-3B cells with IC50 7.55 µg/ml at 72 h. Blank Pd nanoparticles and white tea extract alone had smaller effects on WHEI-3B viability and on normal fibroblasts. Pd@W.tea-NPs increased the proportion of Annexin V-positive WHEI-3B cells and induced G2/M cell cycle arrest. Leukemic cells in the spleen were reduced by Pd@W.tea-NPs with an increase in Bax/Bcl-2 and cytochrome-C protein and mRNA levels indicating the activation of the mitochondrial apoptotic pathway. These effects replicated the effects of ATRA and were not observed using blank Pd nanoparticles. Pd@W.tea-NPs afford therapeutic efficacy against leukemia likely to pivot on activation of the mitochondrial pathway of apoptotic signaling and hence appear attractive potential candidates for development as a novel anticancer agent.

Ameliorative effect of Boesenbergin A, a chalcone isolated from Boesenbergia rotunda (Fingerroot) on oxidative stress and inflammation in ethanol-induced gastric ulcer in vivo.

ETHNOPHARMACOLOGICAL RELEVANCE: Boesenbergia rotunda (L.) Mansf. Kulturpfl., previously known as Boesenbergia pandurata (Family: Zingiberaceae) is a ginger species, locally known as fingerroot. It is an integral part of Southeast Asian traditional medicine in alleviating many gastrointestinal disorders such as flatulence, carminative, stomach ache, dyspepsia, and peptic ulcer. AIM OF THE STUDY: Earlier we have investigated the cytoprotective effect of Boesenbergia rotunda extract. In the present study, we investigated the gastroprotection activity of Boesenbergin A (BA), a chalcone isolated from Boesenbergia rotunda extract in ethanol-induced ulcer model in rats. Besides, the contribution of anti-inflammatory and anti-oxidant ability of BA as probable mechanisms involved in the anti-ulcer activity, also been studied. MATERIALS AND METHODS: BA was orally administered in rats before ulcer induction with ethanol. The lesions of the gastric mucosa were evaluated macroscopically and histopathologically. The efficiency of BA in mucus production, NO production, PGE2 synthesis, mucosal nonprotein sulphydryls, glutathione (GSH) level, and lipid peroxidation (MDA) level were studied. The involvement of the anti-inflammatory capacity of BA was analyzed by using the measurement of cytokines such as TNF-α and IL-6. Finally, the expression of biomarkers such as HSP 70 and iNOS was analyzed at the transcriptional and translational levels. RESULTS: We confirmed the protective capacity of BA via the reduction of ulcerated and haemorrhagic areas. It has induced the protection through lowering GSH, MDA and increased NP-SH level. The plasma NO levels were significantly less in BA treated rats. Both cytokines TNF-α and IL-6 were decreased together with elevated PGE2. Upregulation of HSP and downregulation of iNOS were determined in immunohistochemical and gene expression studies CONCLUSIONS: The current results suggest that the prophylactic effect found with BA is due to (i) boosting of gastric mucus production and suppression of inflammatory mediators, via pro-inflammatory cytokines and (ii) modulating the oxidative stress response. The usefulness of Boesenbergia rotunda in folk medicine in treating ulcers partially could be due to the presence of this chalcone.

Khat Induced Toxicity: Role on Its Modulating Effects on Inflammation and Oxidative Stability.

Long-term khat (Catha edulis Forsk.) chewing has negative effects on human body. Khat constituents appear to be capable of disturbing the delicate equilibrium between damaging and protective mechanisms of a cell that is essential for optimal activity, thereby producing oxidative damage. Therefore, the current study was designed to understand the role of khat on cell toxicity, oxidative stability, and inflammation. Khat was extracted using 60% methanol and assessed calorimetrically for its phenolic and flavonoid contents. 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging, oxygen radical absorbance capacity (ORAC), and ferric reducing/antioxidant power (FRAP) assays were used to assess the antioxidant properties. Lipopolysaccharide and interferon gamma induced murine monocytic macrophages cell line (RAW 264.7) were used to assess khat effects on cellular inflammation, oxidative stability, and viability. Khat possesses high content of polyphenols and flavonoids. The results showed a strong potency of antioxidants in DPPH, ORAC, and FRAP assays. Khat decreases the production of the proinflammatory nitric oxide and induces cytotoxicity and reactive oxygen species inhibition. Heavy khat consumption induced-toxicity and symptoms are probably due the harmful effects of its polyphenolic contents.

An anti-inflammatory molecular mechanism of action of α-mangostin, the major xanthone from the pericarp of Garcinia mangostana: an in silico, in vitro and in vivo approach.

α-Mangostin (αMN) is a xanthone present in the pericarp of Garcinia mangostana Linn. which is mentioned in Ayurveda and is a widely used functional food supplement. However, its anti-inflammatory mechanism is not well studied. Hence, we used in silico, in vitro and in vivo models to provide information of the mechanism on how αMN could prevent inflammation. Firstly, molecular docking was used to find out the binding energy of αMN with NFκB and COX proteins. Secondly, LPS induced RAW 264.7 cells were used to measure the production of cytokines, the prevention of translocation of NFκB and the inhibition of COX-1 and -2 enzymes. Finally, carrageenan-induced peritonitis was used in vivo to check cytokine release, leukocyte migration and vascular permeability. The in silico modelling had showed that αMN has the lowest binding energy with COX-2 and NFκB proteins. αMN has been found to inhibit the production of PGE2 and nitric oxide, and iNOS protein expression. TNF-α and IL-6 cytokines were inhibited significantly (p < 0.05) at 8 and 14 µg ml-1 concentration. αMN at higher doses inhibits the translocation of NFκB together with suppressing the COX-2 enzymes, but not COX-1. αMN inhibited the total leukocyte migration, predominantly, neutrophils in vivo. The level of TNFα and IL-1ß was significantly (p < 0.05) reduced in the peritoneal fluids as measured by ELISA analysis. Taken together, these results demonstrate that αMN acts well as an anti-inflammatory agent via inhibiting the hallmark mechanisms of inflammation. It can be considered as a potential alternative lead compound. In addition, the current results support the traditional use of this fruit pericarp as a functional food.

Beta-mangostin from Cratoxylum arborescens activates the intrinsic apoptosis pathway through reactive oxygen species with downregulation of the HSP70 gene in the HL60 cells associated with a G0/G1 cell-cycle arrest.

Xanthones are phytochemical compounds found in a number of fruits and vegetables. Characteristically, they are noted to be made of diverse properties based on their biological, biochemical, and pharmacological actions. Accordingly, the apoptosis mechanisms induced by beta-mangostin, a xanthone compound isolated from Cratoxylum arborescens in the human promyelocytic leukemia cell line (HL60) in vitro, were examined in this study. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was done to estimate the cytotoxicity effect of ß-mangostin on the HL60 cell line. Acridine orange/propidium iodide and Hoechst 33342 dyes and Annexin V tests were conducted to detect the apoptosis features. Caspase-3 and caspase-9 activities; reactive oxygen species; real-time polymerase chain reaction for Bcl-2, Bax, caspase-3, and caspase-9 Hsp70 genes; and western blot for p53, cytochrome c, and pro- and cleavage-caspase-3 and caspase-9 were assessed to examine the apoptosis mechanism. Cell-cycle analysis conducted revealed that ß-mangostin inhibited the growth of HL60 at 58 µM in 24 h. The administration of ß-mangostin with HL60 caused cell morphological changes related to apoptosis which increased the number of early and late apoptotic cells. The ß-mangostin-catalyzed apoptosis action through caspase-3, caspase-7, and caspase-9 activation overproduced reactive oxygen species which downregulated the expression of antiapoptotic genes Bcl-2 and HSP70. Conversely, the expression of the apoptotic genes Bax, caspase-3, and caspase-9 were upregulated. Meanwhile, at the protein level, ß-mangostin activated the formation of cleaved caspase-3 and caspase-9 and also upregulated the p53. ß-mangostin arrested the cell cycle at the G0/G1 phase. Overall, the results for ß-mangostin showed an antiproliferative effect in HL60 via stopping the cell cycle at the G0/G1 phase and prompted the intrinsic apoptosis pathway.

Beta-mangostin demonstrates apoptogenesis in murine leukaemia (WEHI-3) cells in vitro and in vivo.

BACKGROUND: Beta-mangostin (BM) is a xanthone-type of natural compound isolated from Cratoxylum arborescens. This study aimed to examine the apoptosis mechanisms induced by BM in a murine monomyelocytic cell line (WEHI-3) in vitro and in vivo. METHODS: A WEHI-3 cell line was used to evaluate the cytotoxicity of BM by MTT. AO/PI and Hoechst 33342 dyes, Annexin V, multiparametric cytotoxicity 3 by high content screening (HCS); cell cycle tests were used to estimate the features of apoptosis and BM effects. Caspase 3 and 9 activities, ROS, western blot for Bcl2, and Bax were detected to study the mechanism of apoptosis. BALB/c mice injected with WEHI-3 cells were used to assess the apoptotic effect of BM in vivo. RESULTS: BM suppressed the growth of WEHI-3 cells at an IC50value of 14 ± 3 µg/mL in 24 h. The ROS production was increased inside the cells in the treated doses. Both caspases (9 and 3) were activated in treating WEHI-3 cells at 24, 48 and 72 h. Different signs of apoptosis were detected, such as cell membrane blebbing, DNA segmentation and changes in the asymmetry of the cell membrane. Another action by which BM could inhibit WEHI-3 cells is to restrain the cell cycle at the G1/G0 phase. In the in vivo study, BM reduced the destructive effects of leukaemia on the spleen and liver by inducing apoptosis in leukaemic cells. CONCLUSION: BM exerts anti-leukaemic properties in vitro and in vivo.