Identification of pheophorbide a as an inhibitor of receptor for advanced glycation end products in Mallotus japonicus.

Accumulation of advanced glycation end products (AGEs) plays an important role in diabetes, immunoinflammation, and cardiovascular and neurodegenerative diseases. Since AGEs mediate their pathological effects through interaction with receptor for AGEs (RAGE), RAGE antagonists would provide a useful therapeutic option for various health disorders. Therefore, in this study, we aimed to identify phytochemicals that would inhibit binding of AGEs to RAGE, which may help develop new drug leads and/or nutraceuticals for AGE-RAGE-related diseases. On screening ethanol extracts obtained from 700 plant materials collected in Myanmar, we found that the ethanol extract from the leaves of Mallotus philippensis inhibited the binding of AGEs to RAGE. We also found that the leaves of M. japonicus, which belongs to the same genera and distributes abundantly in Japan, exhibited the inhibitory activity similar to M. philippensis. Activity-guided fractionation and LC/MS analysis of the ethanol extract of M. japonicus helped identify pheophorbide a (PPBa) as a major component in the active fraction, along with some other pheophorbide derivatives. PPBa exhibited potent inhibitory activity against AGE-RAGE binding, with an IC50 value (0.102 µM) comparable to that of dalteparin (0.084 µM). PPBa may be a valuable natural product for use as a therapeutic agent and/or a nutraceutical against various health complications arising from activation of the AGE-RAGE axis.

Enantiomeric chromene derivatives with anticancer effects from Mallotus apelta.

Mallotusapelta(Lour.) Müll.Arg has been used in traditional medicine for the treatment of chronic hepatitis. Six new chromene derivatives, malloapeltas C-H (1-6) and one known compound, malloapelta B (7) were isolated and structured from the leaves of M.apelta. Two pairs of enantiomers (1a/1b and 2a/2b) were successfully separated by chiral high-pressure liquid chromatography (HPLC). The structures and absolute configurations of compounds were determined using spectroscopic methods, including 1D, 2D NMR, and MS and quantum chemical calculation methods. All compounds were evaluated for cytotoxic activity using cell counting kit-8 (CCK-8) assay against ovariancancer cell line (TOV-21G). Compounds 1-5 and 7 exhibited significant growth and viability inhibitory effects with GI50 values ranging from 0.06 to 10.39 µM and IC50 values ranging from 1.62 to 10.42 µM on ovarian cancer cell line, TOV-21G. The most cytotoxic compounds 2, 3, and 7 were chosen for studying in apoptosis mechanism. Compounds 2, 3, and 7-induced apoptosis as evidenced by activated caspase 8, caspase 9, and PARP, increased Bak and Bax, and decreased Bcl-xL and survivin. Moreover, compounds 2, 3, and 7 significantly inhibited the NF-κB signaling pathway. Taken together, our findings propose the potential application of compounds 2, 3, and 7 for treating cancer via modulating NF-κB activity.

Three new triterpenoids from Mallotus macrostachyus.

Three new triterpenoids, mallomacrostins A-C (1-3), and 11 known ones (4-14) were obtained from the twigs and leaves of Mallotus macrostachyus. Mallomacrostin A possessed a new trinor-D:B-friedobaccharane skeleton. The structures of the new compounds were elucidated on the basis of extensive spectroscopic techniques including HR-ESIMS and NMR and the structure of 1 was confirmed by single crystal X-ray diffraction analysis. Spectroscopic data of the known compound 4 were provided for the first time. Compounds 2 and 10 exhibited significant anti-inflammatory activity by inhibiting LPS-induced release of nitric oxide with IC50 of 70.0 µM and 14.0 µM, respectively.

Mallotus oblongifolius extracts ameliorate ischemic nerve damage by increasing endogenous neural stem cell proliferation through the Wnt/ß-catenin signaling pathway.

Mallotus oblongifolius (MO), an edible medicinal plant from Hainan in China, shows a wide range of bioactivities. The daily consumption of MO or its extracts has been observed to ameliorate ischemic nerve injury. However the mechanisms remain unclear. In this study, the effects of MO both in vitro and in vivo were investigated. The results indicated that MO improved the motor ability, neurosensory ability, balance and grasping ability of mice with ischemic injuries, induced by bilateral common carotid artery ligation (BCCAL). In addition, MO improved the morphology of neurons, resisted the loss of neurons, and enhanced the content of the nestin protein in the cerebral cortex and subgranular zone (SGZ) area. Furthermore, in the oxygen-glucose deprivation and reperfusion (OGD/R) treated cell model, MO could effectively activate the Wnt/ß-catenin signaling pathway and promote the proliferation of neural stem cells (NSCs) and increase the protein expression levels of ß-catenin and CyclinD1. Our results suggest that Mallotus oblongifolius may be used as nutraceuticals or functional foods to alleviate ischemic nerve damage and promote recovery from ischemic stroke.

Cytotoxic Activity and Related Mechanisms of Prenylflavonoids Isolated from Mallotus conspurcatus Croizat.

Five prenylflavonoids, 6-prenylnaringenin (1), 8-prenylnaringenin (2), 7-O-methyl-8-prenylnaringenin (3), 7-O-methyl-6-prenylnaringenin (4), and 4'-O-methyl-6-prenylnaringenin (5), were isolated from the traditional herb Mallotus conspurcatus Croizat (Euphorbiaceae). Compounds 1-5 revealed cytotoxic activity against cervical cancer (HeLa) cells with IC50 values ranging from 10.08 to 60.16 µm by MTT method, and interestingly, these prenylflavonoids were less toxic to normal HL-7702 cells. Furthermore, compounds 1 and 5 could inhibit the c-myc expression and telomerase activity and cause mitochondrial dysfunction. These findings might contribute to a better understanding of the biological activities of prenylflavonoids and lay the foundation for further studies on the cytotoxic activity of natural products isolated from M. conspurcatus.

Discovery of anti-inflammatory terpenoids from Mallotus conspurcatus croizat.

ETHNOPHARMACOLOGICAL RELEVANCE: Mallotus conspurcatus croizat (Euphorbiaceae), a plant native to Jinxiu in Guangxi, is popularly used in folk medicine to treat pelvic inflammatory disease. The anti-inflammatory activities of the compounds obtained from M. conspurcatus root were evaluated in this study. AIM OF THE STUDY: This study explored the major anti-inflammatory components of this plant. MATERIALS AND METHODS: The ethyl acetate fraction of the ethanol extract from M. conspurcatus was separated using chromatographic techniques. The structures of the isolates were elucidated from NMR, MS and X-ray data as well as from ECD. The anti-inflammatory activities of the isolates from M. conspurcatus were evaluated using LPS-stimulated RAW 264.7 cell models. The production of NO, TNF-α and PGE-2 was determined by ELISA and Griess tests. The expression levels of COX-2, NF-κB/p65 and iNOS were measured by western blotting. RESULTS: Two new diterpenoids, malloconspur A (1) and malloconspur B (2), and sixteen known terpenoids (3-18) were identified by comprehensive spectroscopic analyses and comparison with literature data. Malloconspur B (2) and 17-hydroxycleistantha-12,15-dien-3-one (3) substantially inhibited the release of NO with IC50 values of 10.47 µM and 9.32 µM, respectively. Compounds 1, 2 and 3 markedly decreased the secretion of PGE2 and TNF-α (P < 0.01) by LPS-induced RAW264.7 cells. Compounds 2 and 3 markedly decreased iNOS, NF-κB/p65 and COX-2 protein expression. CONCLUSIONS: Our identification of these diterpenoids provides strong evidence for the use of M. conspurcatus among the Yao people as a medicinal plant for the treatment of inflammation. The dramatic differences in the chemical structures of the active diterpenoids of this plant from those on the market suggest these compounds have potential as anti-inflammatory lead compounds for follow-up research.

Ancient and modern anticonvulsants act synergistically in a KCNQ potassium channel binding pocket.

Epilepsy has been treated for centuries with herbal remedies, including leaves of the African shrub Mallotus oppositifolius, yet the underlying molecular mechanisms have remained unclear. Voltage-gated potassium channel isoforms KCNQ2-5, predominantly KCNQ2/3 heteromers, underlie the neuronal M-current, which suppresses neuronal excitability, protecting against seizures. Here, in silico docking, mutagenesis and cellular electrophysiology reveal that two components of M. oppositifolius leaf extract, mallotoxin (MTX) and isovaleric acid (IVA), act synergistically to open neuronal KCNQs, including KCNQ2/3 channels. Correspondingly, MTX and IVA combine to suppress pentylene tetrazole-induced tonic seizures in mice, whereas individually they are ineffective. Co-administering MTX and IVA with the modern, synthetic anticonvulsant retigabine creates a further synergy that voltage independently locks KCNQ2/3 open. Leveraging this synergy, which harnesses ancient and modern medicines to exploit differential KCNQ isoform preferences, presents an approach to developing safe yet effective anticonvulsants.

ytotoxic Constituents of Mallotus microcarpus.

A new 3-methoxybenzensulfonic acid 4-0-0-D-glucopyranoside (1), and ten known compounds (2-11) were isolated from the methanolic extract of the stems of Mallotus microcarpus. The cytotoxicity of the isolated compounds was evaluated by the MTT method. 3-Methoxybenzensulfonic acid 4-Ο-ß-D- glucopyranoside (1) and methyl salicylate 2-rutinoside (5) showed strong cytotoxicity against EGFR-TKI-resistant human lung cancer A549 cells in comparison with camptothecin. Compound 1, leonuriside A (2), 3,4'-dihydroxypropiophenone 3-Ο-glucoside (6) and (lR,2S)-hovetrichoside A (10) inhibited the growth of human breast cancer MCF-7 cell line with IC50 values in the range of 0.48-1.78 µM. This is the first report on the chemical composition and cytotoxic activity of M microcarpus.

Cytokine Attenuation and Free Radical Scavenging Activity of a New Flavanone7,4'-Dihydroxy-3″,3″-Dimethyl -(5,6-Pyrano-2″-One)- 8- (3‴,3‴-Dimethyl Allyl)- Isolated from Mallotus philippensis: Possible Mechanism for Its Anti-Inflammatory Activity.

Mallotus philippensis L.(MP) commonly known as Kamala tree in Hindi,is a small to medium-sized monoecious tree.The objective of the study was to evaluate the anti-inflammatory activity of MPand a new flavanoneisolated from it by using in vivo models of inflammation.Albino wistar rats of either sex weighing 150-200g were used. Seven groups were made (n = 6), namely normal control group (normal saline, 1 ml/kg), standard control group (acetylsalicylic acid, 100 mg/kg), methanol crude extract (300 and 500 mg/kg), ethylacetate fraction (300 and 500 mg/kg) and active compound 4 (new flavanone, 50 mg/kg). The anti-inflammatory activity was studied using carrageenan induced paw edema method and cotton pellet granuloma method. Levels of cytokines (TNF-α, IL-1and IL-6) and activity of antioxidant enzymeslike catalase and glutathione peroxidase were estimated. It was found that the methanol extract, ethylacetate fraction and Flavanonedemonstrated significant reduction in paw edema in carrageenan induced paw edema method as compared to control. They also diminished the serum TNF-α, IL-6 and IL-1 levels. Significantly attenuated the malondialdehyde levels and increased the activities of catalase and glutathione peroxidase in paw tissue. Similarly there was asignificant decrease in granuloma formation in cotton pellet induced granuloma method. In conclusion, MP extracts and the newflavanonepossess anti-inflammatory activity and this might be due to the inhibition of various cytokines and increased free radical scavenging activity.

Rottlerin, a polyphenolic compound from the fruits of Mallotus phillipensis (Lam.) Müll.Arg., impedes oxalate/calcium oxalate induced pathways of oxidative stress in male wistar rats.

BACKGROUND: Oxalate and/or calcium oxalate, is known to induce free radical production, subsequently leading to renal epithelial injury. Oxidative stress and mitochondrial dysfunction have emerged as new targets for managing oxalate induced renal injury. HYPOTHESIS: Plant products and antioxidants have gained tremendous attention in the prevention of lithiatic disease. Rottlerin, a polyphenolic compound from the fruits of Mallotus phillipensis (Lam.) Müll.Arg., has shown free radical scavenging, antioxidant activity and has been reported to interfere in signaling pathways leading to inflammation and apoptosis. In this study, the potential role of rottlerin, in rats exposed to hyperoxaluric environment was explored. METHODS: Hyperoxaluria was induced by administering 0.4% ethylene glycol and 1% ammonium chloride in drinking water to male wistar rats for 9 days. Rottlerin was administered intraperitoneally at 1mg/kg/day along with the hyperoxaluric agent. Prophylactic efficacy of rottlerin to diminish hyperoxaluria induced renal dysfunctionality and crystal load was examined along with its effect on free radicals generating pathways in hyperoxaluric rats. RESULTS: 0.4% ethylene glycol and 1% ammonium chloride led to induction of hyperoxaluria, oxiadtive stress and mitochondrial damage in rats. Rottlerin treatment reduced NADPH oxidase activity, prevented mitochondrial dysfunction and maintained antioxidant environment. It also refurbished renal functioning, tissue integrity and diminished urinary crystal load in hyperoxaluric rats treated with rottlerin. CONCLUSIONS: Thus, the present investigation suggests that rottlerin evidently reduced hyperoxaluric consequences and the probable mechanism of action of this drug could be attributed to its ability to quench free radicals by itself and interrupting signaling pathways involved in pathogenesis of stone formation.

Novel R-plasmid conjugal transfer inhibitory and antibacterial activities of phenolic compounds from Mallotus philippensis (Lam.) Mull. Arg.

Antimicrobial resistance severely limits the therapeutic options for many clinically important bacteria. In Gram-negative bacteria, multidrug resistance is commonly facilitated by plasmids that have the ability to accumulate and transfer refractory genes amongst bacterial populations. The aim of this study was to isolate and identify bioactive compounds from the medicinal plant Mallotus philippensis (Lam.) Mull. Arg. with both direct antibacterial properties and the capacity to inhibit plasmid conjugal transfer. A chloroform-soluble extract of M. philippensis was subjected to bioassay-guided fractionation using chromatographic and spectrometric techniques that led to the isolation of the known compounds rottlerin [5,7-dihydroxy-2,2-dimethyl-6-(2,4,6-trihydroxy-3-methyl-5-acetylbenzyl)-8-cinnamoyl-1,2-chromene] and the red compound (8-cinnamoyl-5,7-dihydroxy-2,2,6-trimethylchromene). Both compounds were characterised and elucidated using one-dimensional and two-dimensional nuclear magnetic resonance (NMR). Rottlerin and the red compound showed potent activities against a panel of clinically relevant Gram-positive bacteria, including meticillin-resistant Staphylococcus aureus (MRSA). No significant direct activities were observed against Gram-negative bacteria. However, both rottlerin and the red compound strongly inhibited conjugal transfer of the plasmids pKM101, TP114, pUB307 and R6K amongst Escherichia coli at a subinhibitory concentration of 100mg/L. Interestingly, despite the planar nature of the compounds, binding to plasmid DNA could not be demonstrated by a DNA electrophoretic mobility shift assay. These results show that rottlerin and the red compound are potential candidates for antibacterial drug lead development. Further studies are needed to elucidate the mode of inhibition of the conjugal transfer of plasmids.

Scientific evidence of plant with a rapid-onset and sustained antidepressant effect in a chronic model of depression: Mallotus oppositifolius.

BACKGROUND: One of the major drawbacks of current depression pharmacotherapy is the delay in symptom improvement, aside from the untoward side effects and lack of efficacy against refractory depression. This work therefore investigated a possible rapid-onset and sustained antidepressant effect of Mallotus oppositifolius. METHODS: Onset of the antidepressant effect of hydroalcoholic extract from the leaves of M. oppositifolius was investigated using the open space swim test, a chronic depression model. The possible effects of the extract on cognitive dysfunction measured in the Morris water maze and weight gain were also investigated. RESULTS: M. oppositifolius extract, after the first day of treatment, reversed the state of immobility in mice. This effect was sustained even after drug treatment was halted and the antidepressant effect verified in the tail suspension test. The extract also increased the total distance travelled by the mice and reversed the cognitive impairment induced by the depressed state but had no effect on weight variation. CONCLUSIONS: M. oppositifolius exhibits a rapid-onset and sustained antidepressant effect in mice.

Antioxidant and Antiplasmodial Activities of Bergenin and 11-O-Galloylbergenin Isolated from Mallotus philippensis.

Two important biologically active compounds were isolated from Mallotus philippensis. The isolated compounds were characterized using spectroanalytical techniques and found to be bergenin (1) and 11-O-galloylbergenin (2). The in vitro antioxidant and antiplasmodial activities of the isolated compounds were determined. For the antioxidant potential, three standard analytical protocols, namely, DPPH radical scavenging activity (RSA), reducing power assay (RPA), and total antioxidant capacity (TAC) assay, were adopted. The results showed that compound 2 was found to be more potent antioxidant as compared to 1. Fascinatingly, compound 2 displayed better EC50 results as compared to α-tocopherol while being comparable with ascorbic acid. The antiplasmodial assay data showed that both the compound exhibited good activity against chloroquine sensitive strain of Plasmodium falciparum (D10) and IC50 values were found to be less than 8 µM. The in silico molecular docking analyses were also performed for the determination of binding affinity of the isolated compounds using P. falciparum proteins PfLDH and Pfg27. The results showed that compound 2 has high docking score and binding affinity to both protein receptors as compared to compound 1. The demonstrated biological potentials declared that compound 2 could be the better natural antioxidant and antiplasmodial candidate.

Mallotus roxburghianus modulates antioxidant responses in pancreas of diabetic rats.

Mallotus roxburghianus has long been used by Mizo tribal people for the treatment of diabetes. Scientific validation at known doses may provide information about its safety and efficacy. Methanolic leaf extract of M. roxburghianus (MRME 100 and 400mg/kg) was tested in comparison with normal and alloxan diabetic rats for 28 days p.o. in terms of body and pancreatic weight, blood glucose level, antioxidant enzymes, expression of visfatin and PCNA, histopathology and histomorphometric measurements of pancreas. The results were evaluated statistically using ANOVA, correlation and regression and Principal component analysis (PCO). MRME (100 and 400mg/kg) treatment significantly (p<0.0001) decreased the body weight, blood glucose level, improved the mass and size of pancreas, elevated the levels of antioxidant enzymes and up regulate the expression of visfatin and PCNA. PCO analysis was good to fitness and prediction distinguishes the therapeutic effects of M. roxburghianus from the alloxan induced diabetic rats. MRME has significant role in protecting animals from alloxan-induced diabetic oxidative stress in pancreas and exhibited promising antihyperglycaemic and antioxidant activities along with significant reversal of disturbed antioxidant status and lipid peroxidative damage. Pancreatic architecture and physiology under diabetic oxidative stress have been significantly modulated by MRME and validated as a drug candidate for antidiabetic treatment. M. roxburghianus treatment restores the antioxidant enzyme system and rejuvenates the islets mass in alloxanized rat by accelerating visfatin and PCNA expression in pancreatic tissue.

Bioactive phloroglucinols from Mallotus oppositifolius.

The two new acylphloroglucinol derivatives, methylene-bis-aspidinol AB (1) and mallopposinol (2), together with the nine known compounds, aspidinol B (3), methylene-bis-aspidinol (4), (+)-α-tocopherol (5), lupeol (6), stigmasterol (7), phytol (8), bergenin (9), squalene (11) and methyl gallate (10) were isolated from the leaves of Mallotus oppositifolius. Their structures were elucidated by spectral analysis including MS, 1D and 2D-NMR spectroscopy. In vitro trypanocidal and antileishmanial activities of compounds 1-9 were evaluated. Mallopposinol (2) and aspidinol B (3) displayed weak antileishmanial activities against Leishmania donovani promastigotes, with EC50 values of 21.3 and 38.8µM, respectively. Only the methylene-bis-aspidinol (4) exhibited trypanocidal activity against Trypanosoma brucei brucei trypomastigotes (LC100=0.8µM) similar to the reference drug pentamidine (LC100=0.4µM).

Discrimination and classification techniques applied on Mallotus and Phyllanthus high performance liquid chromatography fingerprints.

Mallotus and Phyllanthus genera, both containing several species commonly used as traditional medicines around the world, are the subjects of this discrimination and classification study. The objective of this study was to compare different discrimination and classification techniques to distinguish the two genera (Mallotus and Phyllanthus) on the one hand, and the six species (Mallotus apelta, Mallotus paniculatus, Phyllanthus emblica, Phyllanthus reticulatus, Phyllanthus urinaria L. and Phyllanthus amarus), on the other. Fingerprints of 36 samples from the 6 species were developed using reversed-phase high-performance liquid chromatography with ultraviolet detection (RP-HPLC-UV). After fingerprint data pretreatment, first an exploratory data analysis was performed using Principal Component Analysis (PCA), revealing two outlying samples, which were excluded from the calibration set used to develop the discrimination and classification models. Models were built by means of Linear Discriminant Analysis (LDA), Quadratic Discriminant Analysis (QDA), Classification and Regression Trees (CART) and Soft Independent Modeling of Class Analogy (SIMCA). Application of the models on the total data set (outliers included) confirmed a possible labeling issue for the outliers. LDA, QDA and CART, independently of the pretreatment, or SIMCA after "normalization and column centering (N_CC)" or after "Standard Normal Variate transformation and column centering (SNV_CC)" were found best to discriminate the two genera, while LDA after column centering (CC), N_CC or SNV_CC; QDA after SNV_CC; and SIMCA after N_CC or after SNV_CC best distinguished between the 6 species. As classification technique, SIMCA after N_CC or after SNV_CC results in the best overall sensitivity and specificity.

Antioxidant capacity and radical scavenging effect of polyphenol rich Mallotus philippenensis fruit extract on human erythrocytes: an in vitro study.

Mallotus philippinensis is an important source of molecules with strong antioxidant activity widely used medicinal plant. Previous studies have highlighted their anticestodal, antibacterial, wound healing activities, and so forth. So, present investigation was designed to evaluate the total antioxidant activity and radical scavenging effect of 50% ethanol fruit glandular hair extract (MPE) and its role on Human Erythrocytes. MPE was tested for phytochemical test followed by its HPLC analysis. Standard antioxidant assays like DPPH, ABTS, hydroxyl, superoxide radical, nitric oxide, and lipid peroxidation assay were determined along with total phenolic and flavonoids content. Results showed that MPE contains the presence of various phytochemicals, with high total phenolic and flavonoid content. HPLC analysis showed the presence of rottlerin, a polyphenolic compound in a very rich quantity. MPE exhibits significant strong scavenging activity on DPPH and ABTS assay. Reducing power showed dose dependent increase in concentration absorption compared to standard, Quercetin. Superoxide, hydroxyl radical, lipid peroxidation, nitric oxide assay showed a comparable scavenging activity compared to its standard. Our finding further provides evidence that Mallotus fruit extract is a potential natural source of antioxidants which have a protective role on human Erythrocytes exhibiting minimum hemolytic activity and this justified its uses in folklore medicines.

A new chromone from the twig of Mallotus apelta.

A new chromone, 7-hydroxy-2-hydroxymethyl-8-methoxy-4-oxo-4H-chromene-6-carboxylic acid, named melachromone, along with 13 known compounds (2-14), including chromones, flavonoids, coumarins and phenylpropane derivatives, were isolated from the twig of Mallotus apelta. Their chemical structures were elucidated by using various spectroscopic methods. Anti-tumour evaluation of the compounds suggested that compound 1 exhibited medium cytotoxic activity against KB and HeLa Cells, with IC50 values of 9.50 and 9.23 µg mL(-1), respectively.

Mallotus philippinensis Muell. Arg (Euphorbiaceae): ethnopharmacology and phytochemistry review.

Mallotus philippinensis Muell. Arg (Euphorbiaceae) are widely distributed perennial shrub or small tree in tropical and subtropical region in outer Himalayas regions with an altitude below 1,000 m and are reported to have wide range of pharmacological activities. Mallotus philippinensis species are known to contain different natural compounds, mainly phenols, diterpenoids, steroids, flavonoids, cardenolides, triterpenoids, coumarins, isocoumarins, and many more especially phenols; that is, bergenin, mallotophilippinens, rottlerin, and isorottlerin have been isolated, identified, and reported interesting biological activities such as antimicrobial, antioxidant, antiviral, cytotoxicity, antioxidant, anti-inflammatory, immunoregulatory activity protein inhibition against cancer cell. We have selected all the pharmacological aspects and toxicological and all its biological related studies. The present review reveals that Mallotus philippinensis is a valuable source of medicinally important natural molecules and provides convincing support for its future use in modern medicine. However, the existing knowledge is very limited about Mallotus philippinensis and its different parts like steam, leaf, and fruit. Further, more detailed safety data pertaining to the acute and subacute toxicity and cardio- and immunotoxicity also needs to be generated for crude extracts or its pure isolated compounds. This review underlines the interest to continue the study of this genus of the Euphorbiaceae.

Mallotus philippinensis bark extracts promote preferential migration of mesenchymal stem cells and improve wound healing in mice.

In the present study, we report the effects of the ethanol extract from Mallotus philippinensis bark (EMPB) on mesenchymal stem cell (MSC) proliferation, migration, and wound healing in vitro and in a mouse model. Chemotaxis assays demonstrated that EMPB acted an MSC chemoattractant and that the main chemotactic activity of EMPB may be due to the effects of cinnamtannin B-1. Flow cytometric analysis of peripheral blood mononuclear cells in EMPB-injected mice indicated that EMPB enhanced the mobilization of endogenous MSCs into blood circulation. Bioluminescent whole-animal imaging of luciferase-expressing MSCs revealed that EMPB augmented the homing of MSCs to wounds. In addition, the efficacy of EMPB on migration of MSCs was higher than that of other skin cell types, and EMPB treatment improved of wound healing in a diabetic mouse model. The histopathological characteristics demonstrated that the effects of EMPB treatment resembled MSC-induced tissue repair. Taken together, these results suggested that EMPB activated the mobilization and homing of MSCs to wounds and that enhancement of MSC migration may improve wound healing.