The potential role of Hypericum perforatum in wound healing: A literature review on the phytochemicals, pharmacological approaches, and mechanistic perspectives.

St. John's Wort, commonly known as Hypericum perforatum L., is a flowering plant in the Clusiaceae family that traditionally been employed for treating anxiety, depression, wounds, burns, sunburn, irritation, and stomach ailments. This review provides a synopsis of H. perforatum L. phytoconstituents and their biological effects, highlighting its beneficial therapeutic properties for dermatological indications, as well as its antioxidant, antimicrobial, anti-inflammatory, and anti-angiogenic activity in various applications including wound healing and skin conditions such as eczema, sun burn and minor burns also spastic paralysis, stiff neck and mood disorders as anti-depressant and nerve pains such as neuralgia. The data were collected from several databases as Web of Science PubMed, ScienceDirect, Scopus and Google Scholar using the terms: "H. perforatum L.", "H. perforatum L. /phytochemistry," and "H. perforatum extracts/wound healing" collected from 1994 to 2023. The findings suggest H. perforatum L. acts through various mechanisms and plays a role in each phase of the wound healing process, including re-epithelialization, angiogenesis, wound contraction, and connective tissue regeneration. H. perforatum L. enhances collagen deposition, decreases inflammation, inhibits fibroblast migration, and promotes epithelialization by increasing the number of fibroblasts with polygonal shape and the number of collagen fibers within fibroblasts. H. Perforatum L. extracts modulate the immune response and reduce inflammation were found to accelerate the wound healing process via inhibition of inflammatory mediators' production like interleukin-6, tumor necrosis factor-α, cyclooxygenase-2 gene expression, and inducible nitric oxide synthase. Thus, H. perforatum L. represents a potential remedy for a wide range of dermatological problems, owing to its constituents with beneficial therapeutic properties. H. perforatum L. could be utilized in the development of novel wound healing therapies.

Antiplasmodial and anticancer activities of xanthones isolated from Garcinia bancana Miq.

This report describes the isolation and characterization of xanthones from Garcinia bancana Miq. and evaluates their antiplasmodial and anticancer activities. Macluraxanthone (1), isojacareubin (2), and gerontoxanthone C (3) were isolated from the stem bark of G. bancana Miq. for the first time. In silico molecular docking studies revealed the hydrogen bonding and steric interactions between xanthones (1-3) and PfLDH/VEGFR2. The in vitro antiplasmodial activity was assayed against the chloroquine-sensitive Plasmodium falciparum strain 3D7 by the lactate dehydrogenase (LDH) method. The anticancer evaluation was evaluated against the A549, MCF-7, HeLa, and B-16 cancer cell lines. Compounds (1) (IC50 8.45-16.71 µM) and (3) (IC50 9.69-14.86 µM) showed more potent anticancer activity than compound (2) (IC50 25.46-31.31 µM), as well for their antiplasmodial activity (4.28 µM, 5.52 µM, 11.45 µM). Our findings indicated the potential of G. bancana Miq. as a natural resource of antiplasmodial and anticancer compounds.

Garcinia mangostana L. Pericarp Extract and Its Active Compound α-Mangostin as Potential Inhibitors of Immune Checkpoint Programmed Death Ligand-1.

α-Mangostin, a major xanthone found in mangosteen (Garcinia mangostana L., Family Clusiaceae) pericarp, has been shown to exhibit anticancer effects through multiple mechanisms of action. However, its effects on immune checkpoint programmed death ligand-1 (PD-L1) have not been studied. This study investigated the effects of mangosteen pericarp extract and its active compound α-mangostin on PD-L1 by in vitro and in silico analyses. HPLC analysis showed that α-mangostin contained about 30% w/w of crude ethanol extract of mangosteen pericarp. In vitro experiments in MDA-MB-231 triple-negative breast cancer cells showed that α-mangostin and the ethanol extract significantly inhibit PD-L1 expression when treated for 72 h with 10 µM or 10 µg/mL, respectively, and partially inhibit glycosylation of PD-L1 when compared to untreated controls. In silico analysis revealed that α-mangostin effectively binds inside PD-L1 dimer pockets and that the complex was stable throughout the 100 ns simulation, suggesting that α-mangostin stabilized the dimer form that could potentially lead to degradation of PD-L1. The ADMET prediction showed that α-mangostin is lipophilic and has high plasma protein binding, suggesting its greater distribution to tissues and its ability to penetrate adipose tissue such as breast cancer. These findings suggest that α-mangostin-rich mangosteen pericarp extract could potentially be applied as a functional ingredient for cancer chemoprevention.

A new chromanone acid derivative from the nut oil resin of Calophyllum inophyllum.

One novel chromanone acid derivative, namely inocalophylline C (1), together with one known compound calophyllolide (2), were isolated from the methanolic extract of nut oil resin of Calophyllum inophyllum L., a medicinal plant widely distributed in Vietnam. The isolated compound structures were elucidated by spectroscopic methods and the absolute configuration of 1 was established by the single-crystal X-ray crystallography as ethyl (R) 3-((2 R,3R,6R)-4-hydroxy-2,3-dimethyl-6-((R)-5-methyl-2-(prop-1-en-2-yl)hex-4-en-1-yl)-6-(3-methylbut-2-en-1-yl)-5,7-dioxo-3,5,6,7-tetrahydro-2H-chromen-8-yl)-3-phenylpropanoate.

Constituents of the Stem Bark of Symphonia globulifera Linn. f. with Antileishmanial and Antibacterial Activities.

The chemical investigation of the n-hexane fraction from the methanol extract of the stem bark of Symphonia globulifera Linn f., which displayed good in vitro activity against Leishmania donovani NR-48822 promastigotes (IC50 43.11 µg/mL), led to the isolation of three previously unreported polyprenylated benzophenones, guttiferone U (1), V (2)/W (3), and a new tocotrienol derivative named globuliferanol (4), along with 11 known compounds (5-15). Their structures were elucidated based on their NMR and MS data. Some isolated compounds were assessed for both their antileishmanial and cytotoxic activities against L. donovani and Vero cells, respectively. Guttiferone K (5) exhibited the best potency (IC50 3.30 µg/mL), but with low selectivity to Vero cells. The n-hexane fraction and some compounds were also assessed in vitro for their antibacterial activity against seven bacterial strains. All the samples exhibited moderate to potent antibacterial activity (MICs ≤ 15.6 µg/mL) against at least one of the tested strains.

A Comprehensive Review of the Phytochemical and Pharmacological Potential of an Evergreen Plant Garcinia cowa.

Garcinia cowa of the Clusiaceae family, native to South-East Asia used in traditional medicine. It has antipyretic, antimicrobial, and many other biological activities. In this review, a thorough study of this plant's chemical constituents and pharmacological and therapeutic effects was conducted from the research articles from PubMed, Science Direct, Google Scholar, and Scopus from 1977 to 2022. Reported secondary metabolites are enriched with xanthones, phloroglucinols, depsidones, steroids, etc. α-mangostin, ß-mangostin, cowaxanthone, rubraxanthone, cowanin, norcowanin, etc. represent the major xanthones. This article discusses the relationship between the different functional groups in xanthone compounds and their bioactivity against cancer, diabetes, bacteria, leishmania, malaria, and inflammation. This review is a comprehensive compendium of major bioactive molecules and its implication for human disease.

Hyperforin: A natural lead compound with multiple pharmacological activities.

Hypericum perforatum L. (Clusiaceae), commonly known as St. John's wort, has a rich historical background as one of the oldest and most widely studied herbal medicines. Hyperforin is the main antidepressant active ingredient of St. John's wort. In recent years, hyperforin has attached increasing attention due to its multiple pharmacological activities. In this review, the information on hyperforin was systematically summarized. Hyperforin is considered to be a lead compound with diverse pharmacological activities including anti-depression, anti-tumor, anti-dementia, anti-diabetes and others. It can be obtained by extraction and synthesis. Further pharmacological studies and more precise detection methods will help develop a value for hyperforin. In addition, structural modification and pharmaceutical preparation technology will be beneficial to promoting the research progress of hyperforin based innovative drugs. Although these works are full of known and unknown challenges, researchers are still expected to make hyperforin play a greater value.

Discovery of Undescribed Monoterpenoid Polyprenylated Acylphloroglucinols with Immunosuppressive Activities from Hypericum longistylum.

Acylphlorostylums A-G (1-7), seven undescribed monoterpenoid polyprenylated acylphloroglucinols, were isolated and identified from Hypericum longistylum. Significantly, acylphlorostylums A and B were the first monoterpenoid polyprenylated acylphloroglucinols possessing a dodecahydro-1H-benzo [b]cyclopenta [e]oxepine moiety bearing a 6/7/5 fused tricyclic ring system that assembled by the attack from 4-OH to C-13. In addition, acylphlorostylums A-G exhibited moderate in vitro immunosuppressive activity in anti-CD3/anti-CD28 monoclonal antibodies, lipopolysaccharide and concanavalin A-induced murine splenocyte proliferation, with IC50 values ranging from 1.51 ± 0.12 to 18.49 ± 1.67 µM, underscoring those isolates as novel chemical templates in the development of novel immunosuppressors.

Effectiveness and Anticancer Activity of a Novel Phenolic Compound from Garcinia porrecta Against the MCF-7 Breast Cancer Cell Line in vitro and in silico.

BACKGROUND: Cancer is a leading cause of death worldwide, with breast cancer being the most common invasive cancer type in women. Several therapeutic strategies have been explored to reduce the mortality rates of breast cancer. Chemotherapy is the most commonly used systemic treatment, but associated with numerous side-effects. Development of anticancer agents with high efficacy and minimal negative effects is therefore an important focus of research. Natural materials provide an excellent source of bioactive compounds. For instance, Garcinia porrecta from the Clusiaceae family has multiple pharmacological activities, including antioxidant, anti-inflammatory, antibacterial, antiviral, anti-HIV, antidepressant, and anticancer properties. PURPOSE: The main objective of this study was to investigate the potential anticancer effects of compounds extracted from the bark of G. porrecta. MATERIALS AND METHODS: Our experiments were divided into three steps: (1) chromatographic isolation of compounds using various separation techniques, such as extraction, separation and purification, (2) characterization via infrared (IR), nuclear magnetic resonance (NMR) and mass spectroscopy, and (3) evaluation of anticancer activity in vitro (MTT assay) and in silico (via analysis of molecular docking against caspase-9, tumor necrosis factor alpha (TNF-α), estrogen receptor alpha (ER-α), and human epidermal growth factor receptor 2 (HER-2)). RESULTS: Depsidone (1) and benzophenone (2) from the ethyl acetate extract of bark of G. porrecta were identified as bioactive components. Examination of the activities of these compounds against MCF-7 cells revealed an IC50 value of 119.3 µg/mL for benzophenone, whereas IC50 for depsidone could not be estimated. Benzophenone activity was lower than that of the positive control doxorubicin (6.9 µg/mL). Depsidone showed the highest binding affinity for HER-2 (-9.2 kcal.mol-1) and benzophenone for ER-α (-8.0 kcal.mol-1). CONCLUSION: Benzophenone displays potency as an anticancer agent through blocking ER-α.

Polyprenylated acylphloroglucinol meroterpenoids with PTP1B inhibition from Hypericum forrestii.

Three new polyprenylated acylphloroglucinol meroterpenoids, hyperiforins A-C (1-3), were isolated from Hypericum forrestii (Chittenden) N. Robson, together with twelve known analogues (4-15). Their structures were established by extensive physical and spectroscopic data analysis. Compounds 1, 2, 5, 7, and 13-15 showed potent inhibitory effects on protein tyrosine phosphatase 1B with IC50 values from 6.63 ± 2.40 to 14.21 ± 3.51 µM.

Acmoxanthones A-E, New Lavandulated Xanthones from Hypericum acmosepalum N. Robson.

Acmoxanthones A-E (1-5), five new lavandulylated xanthones, were isolated from the aerial parts of Hypericum acmosepalum, together with four known xanthones. Their structures with absolute configurations were elucidated on the basis of analysis of MS, NMR and chiroptical properties. A bioassay against high glucose-induced damage on human umbilical vein endothelial cells (HUVECs) showed ananixanthone (6) and osajaxanthone (7) had potential antioxidative damage activity with EC50 values of 10.5 µg/mL and 7.6 µg/mL, respectively, while 3-hydroxy-2,4-dimethoxyxanthone (8) exhibited cytotoxic effect on the damaged cells with IC50 values of 7.1 µg/mL.

Four new xanthones and their cytotoxicity from the stems of Garcinia schomburgkiana.

Four new xanthones, named schomburgones C-F (1‒4), along with six known xanthones (5‒10) were isolated from the stems of Garcinia schomburgkiana. Their structures were determined by spectroscopic analysis especially 1D and 2D NMR spectroscopies. The isolated compounds were evaluated for their cytotoxicity against five human cancer cell lines. Furanoxanthones 4‒6 showed potent cytotoxicity against four cell lines (KB, HeLa S3, MCF-7 and Hep G2) with IC50 values in the range of 0.18‒9.95 µM.

Structurally diverse polyprenylated acylphloroglucinols from Hypericum uralum Buch.-Ham. ex D. Don.

Uralins A - D, four undescribed polycyclic polyprenylated acylphloroglucinols (PPAPs) featuring an unprecedented fused hexacyclic architecture, a unique monocyclic tetra-seco-tetranor-b-PPAP, an oxidative b-PPAP and a rare norspiroindane-type m-PPAP, respectively, were isolated from the aerial parts of Hypericum uralum, along with ten known PPAPs. Their structures and absolute configurations were elucidated by extensive spectroscopic techniques (MS, NMR, [α]D, CD), conceivable biogenetic pathways and time-dependent density functional theory-based electronic circular dichroism (TDDFT-ECD) calculations. Biological assays showed three b-PPAPs had moderate antioxidative damage activities, while spiroindanes exhibited moderate cytotoxic effects.

Garcinoxanthones SV, new xanthone derivatives from the pericarps of Garcinia mangostana together with their cytotoxic and antioxidant activities.

Xanthones (9H-xanthene-9-ones) are considered to be very promising compounds due to a variety of interesting biological and pharmacological activities. In this study, column chromatography of the methanol extract of the Garcinia mangostana L. pericarps resulted in the isolation of four new xanthones (garcinoxanthones SV, 1-4) and five known analogs including garcinone E (5), 11-hydroxy-1-isomangostin (6) mangostenone E (7), 1,3,6,7-tetrahydroxyxanthone (8), and α-mangostin (9). The structures of the new compounds were elucidated by NMR, HRESIMS, and ECD spectra. Compound 8 (1,3,6,7-tetrahydroxyxanthone) was found from the G. mangostana pericarps for the first time. All the isolated compounds (1-8) were evaluated for their 2,2-diphenyl-1-picrylhydrazyl (DPPH) scavenging capacity and cytotoxicity in vitro against three human cancer cell lines including SK-LU-1, MCF7, and HT-29 cell lines. Compounds 3, 5, and 8 exhibited significant DPPH scavenging capacity with IC50 values of 68.55, 63.05, and 28.45 µM, respectively, in comparison with ascorbic acid (IC50 = 48.03 µM). Compounds 5 and 8 showed moderate cytotoxic effects against the three human cancer cell lines with IC50 value ranges of 19.86-27.38 µM.

Novel polyprenylated benzophenone derivatives from Clusia burle-marxii.

Three new caged polyprenylated benzophenone derivatives named burlemarxiones D-F (1-3) were isolated from the hexane extract of Clusia burle-marxii trunks. Burlemarxione D (1) contains the tetracyclo[8.3.1.03,11.05,10]tetradecane core skeleton also observed for burlemarxione A, its probable immediate precursor. However, two additional rings are formed to produce an unprecedented complex-caged core skeleton. These additional rings could be formed by a radical cyclization reaction of one prenyl group at C-5 with C-1 and C-33, followed by oxidative dehydrogenation (rearomatization) or by an intramolecular [4 + 2] radical cycloaddition (Diels-Alder reaction), followed by an enolization reaction (rearomatization). Burlemarxiones E and F were isolated after methylation with diazomethane that was necessary to avoid the interconversion of the pair of ß-diketones in tautomeric equilibrium. The proposed biosynthetic pathway for burlemarxiones D-F involves the condensation of either lavandulyl pyrophosphate or 2-(1-methylvinyl)-hexa-5-enyl pyrophosphate with the acylphloroglucinol derivative 6-benzoyl-5-hydroxy-5-cyclohexen-1,3-dione, followed by consecutive prenylation reactions. Therefore, Clusia burle-marxii reinforces the claim that the genus Clusia is an important source of sophisticated caged polyprenylated benzophenone derivatives.

Medicinal Potential of Garcinia Species and Their Compounds.

Garcinia is a genus of Clusiaceae, distributed throughout tropical Asia, Africa, New Caledonia, Polynesia, and Brazil. Garcinia plants contain a broad range of biologically active metabolites which, in the last few decades, have received considerable attention due to the chemical compositions of their extracts, with compounds which have been shown to have beneficial effects in several diseases. Our work had the objective of reviewing the benefits of five Garcinia species (G. brasiliensis, G. gardneriana, G. pedunculata, G. cambogia, and G. mangstana). These species provide a rich natural source of bioactive compounds with relevant therapeutic properties and anti-inflammatory effects, such as for the treatment of skin disorders, wounds, pain, and infections, having demonstrated antinociceptive, antioxidant, antitumoral, antifungal, anticancer, antihistaminic, antiulcerogenic, antimicrobial, antiviral, vasodilator, hypolipidemic, hepatoprotective, nephroprotective, and cardioprotective properties. This demonstrates the relevance of the genus as a rich source of compounds with valuable therapeutic properties, with potential use in the prevention and treatment of nontransmissible chronic diseases.

Polyprenylated benzophenone derivatives with a novel tetracyclo[8.3.1.03,11.05,10]tetradecane core skeleton from Clusia burle-marxii exhibited cytotoxicity against GL-15 glioblastoma-derived human cell line.

Three new polyprenylated benzophenone derivatives (1-3) were identified in the hexane extract of Clusia burle-marxii trunks, through the isolation and structural elucidation of their methyl derivatives, along with two known polyprenylated benzophenone derivatives sampsonine N (4) and obdeltifolione C (5). Burlemarxiones A (1) and B (2) show an unprecedent tetracyclo[8.3.1.03,11.05,10]tetradecane core skeleton. These compounds are a pair of ß-diketones in tautomeric equilibrium, whereas isonemorosonol (3) is the respective ß-diketone pair in tautomeric equilibrium with nemorosonol. Burlemarxione A methyl derivative (1a) and sampsonine N exhibited strong in vitro cytotoxic activity against GL-15 glioblastoma-derived human cell line.

Mangostanaxanthone VIII, a new xanthone from Garcinia mangostana and its cytotoxic activity.

A new prenylated xanthone, mangostanaxanthone VIII (7) and six known metabolites: gartanin (1), 1,3,8-trihydroxy-2-(3-methyl-2-butenyl)-4-(3-hydroxy-3-methylbutanoyl)-xanthone (2), rubraxanthone (3), 1,3,6,7-tetrahydroxy-8-prenylxanthone (4), garcinone C (5), and xanthone I (9-hydroxycalabaxanthone) (6) were separated from the EtOAc-soluble fraction of the air-dried pericarps of Garcinia mangostana (Clusiaceae). Their structures have been verified on the basis of spectroscopic data analysis as well as comparison with the literature. The cytotoxic activity of 7 was assessed against MCF7, A549, and HCT116 cell lines using sulforhodamine B (SRB) assay. Compound 7 showed significant cytotoxic potential against MCF7 and A549 cell lines with IC50s 3.01 and 1.96 µM, respectively compared to doxorubicin (0.06 and 0.44 µM, respectively). However, it exhibited moderate activity towards HCT116 cell line.

Guttiferone BL with antibacterial activity from the fruits of Allanblackia gabonensis.

Allanblackia genus, an endless source of bioactive compounds, was investigated for its antibacterial properties. The chemical study of the methanol extract from the fruits of Allanblackia gabonensis resulted in the isolation of the undescribed guttiferone BL (1) along with the known kaempferol (2), morelloflavone (3), morelloflavone 7″-O-ß-D-glucopyranoside (4), ß-sitosterol 3-O-ß-D-glucopyranoside and ß-sitosterol. Their structures were determined using spectrometry and spectroscopic techniques. The antibacterial activity was evaluated against five Gram-negative and two Gram-positive strains using a broth micro-dilution method. Compounds displayed low to significant activity against the tested bacterial strains with MICs ranging from 8 to 512 µg/mL. Morelloflavone (3) presented significant activity against E. coli ATCC8739 (MIC = 8 µg/mL) while guttiferone BL (1) exhibited low activity (MICs = 256-512 µg/mL) against all the tested strains. The crude extract also had moderate to significant activity against the tested bacterial strains.

Two new xanthones and cytotoxicity from the bark of Garcinia schomburgkiana.

Two new xanthone derivatives, named schomburgones A (1) and B (2), along with eight known compounds, including xanthones (3-8) and anthraquinones (9-10) were isolated from the bark of Garcinia schomburgkiana. Their structures were determined by spectroscopic analysis especially 1D and 2D NMR spectroscopies. All isolated compounds were evaluated for their cytotoxicity against five cancer cell lines (KB, HeLa S-3, HT-29, MCF-7 and HepG-2). Compounds 3-6 and 8 showed good cytotoxicity against all the five cancer cell lines with IC50 values in the range of 1.45-9.46 µM.