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.

The Chemical Composition and Transcriptome Analysis Reveal the Mechanism of Color Formation in Tea (Camellia sinensis) Pericarp.

To elucidate the molecular mechanisms underlying the differential metabolism of albino (white), green, and purple pericarp coloration, biochemical profiling and transcriptome sequencing analyses were performed on three different tea pericarps, Zhongbaiyihao (Camellia sinensis L. var. Zhongbai), Jinxuan (Camellia sinensis L. var. Jinxuan), and Baitangziya (Camellia sinensis L. var. Baitang). Results of biochemical analysis revealed that low chlorophyll content and low chlorophyll/carotene ratio may be the biochemical basis for albino characteristics in the 'Zhongbaiyihao' pericarp. The differentially expressed genes (DEGs) involved in anthocyanin biosynthesis, including DFR, F3'5'H, CCoAOMT, and 4-coumaroyl-CoA, were highly expressed in the purple 'Baitangziya' pericarp. In the chlorophyll synthesis of white pericarp, GUN5 (Genome Uncoupled 5) and 8-vinyl-reductase both showed high expression levels compared to the green one, which indicated that albino 'Zhongbaiyihao' pericarp had a higher chlorophyll synthesis capacity than 'Jinxuan'. Meanwhile, chlorophyllase (CLH, CSS0004684) was lower in 'Baitang' than in 'Jinxuan' and 'Zhongbaiyihao' pericarp. Among the differentially expressed transcription factors, MYB59, WRKY41-like2 (CS ng17509), bHLH62 like1 (CS ng6804), and bHLH62-like3 (CSS0039948) were downregulated in Jinxuan pericarp, suggesting that transcription factors played a role in regulating tea pericarp coloration. These findings provide a better understanding of the molecular mechanisms and theoretical basis for utilizing functional components of tea pericarp.

Sonoprocessing improves phenolics profile, antioxidant capacity, structure, and product qualities of purple corn pericarp extract.

For the first time, purple corn pericarp (PCP) was converted to polyphenol-rich extract using two-pot ultrasound extraction technique. According to Plackett-Burman design (PBD), the significant extraction factors were ethanol concentration, extraction time, temperature, and ultrasonic amplitude that affected total anthocyanins (TAC), total phenolic content (TPC), and condensed tannins (CT). These parameters were further optimized using the Box-Behnken design (BBD) method for response surface methodology (RSM). The RSM showed a linear curvature for TAC and a quadratic curvature for TPC and CT with a lack of fit > 0.05. Under the optimum conditions (ethanol (50%, v/v), time (21 min), temperature (28 °C), and ultrasonic amplitude (50%)), a maximum TAC, TPC, and CT of 34.99 g cyanidin/kg, 121.26 g GAE/kg, and 260.59 of EE/kg, respectively were obtained with a desirability value 0.952. Comparing UAE to microwave extraction (MAE), it was found that although UAE had a lower extraction yield, TAC, TPC, and CT, the UAE gave a higher individual anthocyanin, flavonoid, phenolic acid profile, and antioxidant activity. The UAE took 21 min, whereas MAE took 30 min for maximum extraction. Regarding product qualities, UAE extract was superior, with a lower total color change (ΔE) and a higher chromaticity. Structural characterization using SEM showed that MAE extract had severe creases and ruptures, whereas UAE extract had less noticeable alterations and was attested by an optical profilometer. This shows that ultrasound, might be used to extract phenolics from PCP as it requires lesser time and improves phenolics, structure, and product qualities.

Nutrients, Phytochemicals and In Vitro Disease Prevention of Nephelium hypoleucum Kurz Fruit.

Nephelium hypoleucum Kurz is an evergreen tree in the Sapindaceae family, mostly found in the forests of some Southeast Asia countries, especially Thailand. The lack of biological information regarding this tree has led to inappropriate agricultural management, conservation and utilization. Thus, this study aims to examine the nutritional composition, organic acid and phenolic profiles and in vitro health properties through several key enzyme inhibitions against some civilization diseases including Alzheimer's disease (ß-secretase (BACE-1), butyrylcholinesterase (BChE) and acetylcholinesterase (AChE)), obesity (lipase), hypertension (angiotensin-converting enzyme (ACE)) and diabetes (dipeptidyl peptidase-IV (DPP-IV), α-amylase and α-glucosidase) on the aril (flesh) part of N. hypoleucum Kurz fruit. The remaining fruit parts including the pericarp (peel) and seed were also assessed as sources of potential phenolics as well as key enzyme inhibitors. As results, carbohydrate (17.18 g) was found to be a major source of energy (74.80 kcal) in the aril (100 g fresh weight), with trace amounts of protein (0.78 g) and fat (0.32 g). The fruit aril also contained high insoluble dietary fiber (5.02 g) and vitamin C (11.56 mg), while potassium (215.82 mg) was detected as the major mineral. Organic acid profile indicated that the aril was rich in citric acid, while the phenolic profile suggested predominant quercetin and kaempferol. Interestingly, high gallic acid contents were detected in both pericarp and seed, with the latter 3.2-fold higher than the former. The seed also possessed the highest total phenolic content (TPC, 149.45 mg gallic acid equivalent/g dry weight), while total anthocyanin content (TAC, 0.21 mg cyanidin-3-O-glucoside equivalent/g dry weight) was only detected in pericarp. High TPC also led to high enzyme inhibitory activities in seed including BACE-1, AChE, BChE, ACE, DPP-IV and α-glucosidase. Interestingly, aril with the highest α-amylase inhibition suggested strong inhibitory distribution, predominantly from quercetin and kaempferol. Lipase inhibitory activities were only detected in the aril and pericarp, suggesting the biological function of these two phenolics and possibly anthocyanins.

Ultrasound-assisted green extraction methods: An approach for cosmeceutical compounds isolation from Macadamia integrifolia pericarp.

This study aimed was to examine the potential of several green extraction methods to extract cosmetic/cosmeceutical components from Macadamia integrifolia pericarps, which were a by-product of the macadamia nut industry. M. integrifolia pericarps were extracted by conventional solvent extraction process using 95% v/v ethanol and various green extraction methods, including infusion, ultrasound, micellar, microwave, and pulsed electric field extraction using water as a clean and green solvent. The extracts were evaluated for total phenolic content using Folin-Ciocalteu method.The antioxidant activities were evaluated by 1,1-diphenyl-2-picrylhydrazyl (DPPH), 2,2'-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), ferric reducing/antioxidant power, and ferric-thiocyanate method. The anti-skin ageing activities were investigated by means of collagenase, elastase, and hyaluronidase inhibition using enzyme-substrate reaction assay. The irritation profile of the extracts was evaluated by the hen's egg test-chorioallantoic membrane (HET-CAM) test. The results noted that ultrasound-assisted extraction yielded the significantly highest extract amount with the significantly highest total phenolic content (p < 0.05), especially when the extraction time was 10 min. The aqueous extract from ultrasound-assisted extraction possessed the most potent antioxidant and anti-skin ageing activities (p < 0.05). Its antioxidant activities were comparable to ascorbic acid and Trolox, whereas the anti-skin ageing activities were equivalent to epigallocatechin-3-gallate and oleanolic acid. Besides, the extract was safe since it induced no irritation in the HET-CAM test. Therefore, ultrasound-assisted extraction was suggested as an environmentally friendly extraction method for M. integrifolia pericarp extraction and further application in the cosmetic/cosmeceutical industries.

Metatranscriptome Profiling of a Specialized Microbial Consortium during the Degradation of Nixtamalized Maize Pericarp.

Lignocellulose degradation by microbial consortia is multifactorial; hence, it must be analyzed from a holistic perspective. In this study, the temporal transcriptional activity of consortium PM-06, a nixtamalized maize pericarp (NMP) degrader, was determined and related to structural and physicochemical data to give insights into the mechanism used to degrade this substrate. Transcripts were described in terms of metabolic profile, carbohydrate-active enzyme (CAZyme) annotation, and taxonomic affiliation. The PM-06 gene expression pattern was closely related to the differential rates of degradation. The environmental and physiological conditions preceding high-degradation periods were crucial for CAZyme expression. The onset of degradation preceded the period with the highest degradation rate in the whole process, and in this time, several CAZymes were upregulated. Functional analysis of expressed CAZymes indicated that PM-06 overcomes NMP recalcitrance through modular enzymes operating at the proximity of the insoluble substrate. Increments in the diversity of expressed modular CAZymes occurred in the last stages of degradation where the substrate is more recalcitrant and environmental conditions are stressing. Taxonomic affiliation of CAZyme transcripts indicated that Paenibacillus macerans was fundamental for degradation. This microorganism established synergistic relationships with Bacillus thuringiensis for the degradation of cellulose and hemicellulose and with Microbacterium, Leifsonia, and Nocardia for the saccharification of oligosaccharides. IMPORTANCE Nixtamalized maize pericarp is an abundant residue of the tortilla industry. Consortium PM-06 efficiently degraded this substrate in 192 h. In this work, the temporal transcriptional profile of PM-06 was determined. Findings indicated that differential degradation rates are important sample selection criteria since they were closely related to the expression of carbohydrate-active enzymes (CAZymes). The initial times of degradation were crucial for the consumption of nixtamalized pericarp. A transcriptional profile at the onset of degradation is reported for the first time. Diverse CAZyme genes were rapidly transcribed after inoculation to produce different enzymes that participated in the stage with the highest degradation rate in the whole process. This study provides information about the regulation of gene expression and mechanisms used by PM-06 to overcome recalcitrance. These findings are useful in the design of processes and enzyme cocktails for the degradation of this abundant substrate.

Dynamic variation of the phytochemical and volatile compounds in the pericarp of Citrus reticulata ''Chachi'' (Rutaceae) during 2 years of storage.

The pericarp of Citrus reticulata "Chachi" (CRCP) is used as nutritional food and traditional medicine in China, usually harvested at three periods, namely, immature (CRCP-G1), semi-mature (CRCP-G2), and fully mature (CRCP-G3). Traditionally, if the CRCP is stored for a longer period, then the quality will be better. In this study, the dynamic variation of phytochemical and volatile compounds was profiled in the same batches of CRCP during 2 years of storage. Results illustrated that most of the phytochemical compounds showed a decreasing trend during storage, that is, total flavonoids, total phenolic acids, hesperidin, 3,5,6,7,8,3',4'-heptamethoxyflavone, 5-hydroxy-6,7,8,3',4'-pentamethoxyflavone, synephrine, and limonin. The ferulic acid increased significantly, whereas no significant changes were observed in the total polymethoxyflavones, nobiletin, and tangeretin after 2 years of storage. In addition, we found that the extraction yield of volatile oil decreased significantly in CRCP-G1 during storage, and the herb odors were enhanced with the increase of phenols and esters. No significant difference in the extraction yield of volatile oil of CRCP-G2 and CRCP-G3 was found after 2 years of storage, but the citrus-like notes were increased with the promoted generation of alkenes. In particular, the multivariate statistical analysis indicated that 7 volatiles showed a higher level after 1 year of storage, whereas 11 volatiles decreased and 4 volatiles increased after 2 years of storage, respectively. This study could show the early aging mechanism of CRCP harvested at different periods and provide a scientific guidance in the storage of CRCP. PRACTICAL APPLICATION: This study indicated a comprehensive method for rapid analysis of phytochemical and volatile compounds in pericarp of Citrus reticulata ''Chachi'' (Rutaceae) (CRCP) harvested at different periods during 2 years of storage. The results obtained from this study would be valuable for revealing the early aging mechanism and sustainable storage of CRCP.

Decellularization of caprine esophagus using fruit pericarp extract of Sapindus mukorossi.

Biological detergents like sodium deoxycholate, sodium dodecyl sulphate and Triton X-100 impairs the collagenous and non-collagenous proteins, glycosaminoglycans and growth factors. Further, certain chemical and enzymes are responsible for residual cytotoxicity in the decellularized extracellular matrix. The main focus of this study was to explore the decellularization property of soap nut pericarp extract (SPE) for development of decellularized tubular esophageal scaffold. For this 2.5, 5.0 and 10% concentrations of SPE were used for decellularization of caprine esophageal tissues. Histological analysis of hematoxylin and eosin and Masson's trichrome stained tissue samples confirmed decellularization with preservation of extracellular matrix microarchitecture. Scanning electron microscopic images of luminal surface of decellularized esophageal matrix showed randomly oriented collagen fibres with large interconnected pores and cells were absent. However, the external surface was more textured with fibrous structures and collagen fibres were well preserved. DAPI stained decellularized tissues revealed complete removal of nuclear components, verified by DNA content measurement and SDS-PAGE. The FTIR spectra of decellularized esophagus shows absorption peaks of amide A, B, I, II and III. Elastic modulus of the decellularized esophagus scaffolds increased (P > 0.05) as compared to native tissues. Histological and scanning electron microscopic evaluation of in vitro seeded scaffolds showed attachment and growth of primary chicken embryo fibroblasts over and within the decellularized scaffolds. It was concluded that 5% SPE is ideal for preparation of cytocompatible decellularized caprine esophageal scaffold with well-preserved extracellular matrix architecture and, may be used as an alternative to biological detergents and other chemicals.

Comparative Study of Bioactivity and Safety Evaluation of Ethanolic Extracts of Zanthoxylum schinifolium Fruit and Pericarp.

The fruit and pericarp of Zanthoxylum schinifolium (ZS) have been used in traditional medicine; however, few studies have characterized ZS fruit and pericarp. Therefore, in the present study, we evaluated the safety of ZS fruit (ZSF) and pericarp (ZSP) extracts and compared their bioactivity. To evaluate the safety of ZSF and ZSP, mutagenicity, cytotoxicity, and oxidative stress assays were performed and nontoxic concentration ranges were obtained. ZSP was found to be superior to ZSF in terms of its antimutagenic, antioxidant, and anti-inflammatory activities. In the S9 mix, the mutation inhibition rate of ZSP was close to 100% at concentrations exceeding 625 µg·plate-1 for both the TA98 and TA100 strains. ZSP exhibited efficient DPPH (IC50 = 75.6 ± 6.1 µg·mL-1) and ABTS (IC50 = 57.4 ± 6 µg·mL-1) scavenging activities. ZSP inhibited the release of cytokines, involved in IL-1ß (IC50 = 134.4 ± 7.8), IL-6 (IC50 = 262.8 ± 11.2), and TNF-α (IC50 = 223.8 ± 5.8). These results indicate that ZSP contains a higher amount of biochemicals than ZSF, or that ZSP contains unique biochemicals. In conclusion, for certain physiological activities, the use of ZSP alone may be more beneficial than the combined use of ZSF and ZSP.

[Purification and component identification of total proanthocyanidins in Choerospondias axillaris pericarp].

The present study determined the quantitative markers of total proanthocyanidins in the purification of the industrial waste Choerospondias axillaris pericarp based on the comparison results of high-performance liquid chromatography(HPLC) and mass spectrometry(MS) and optimized the purification process with two stable procyanidins as markers. The adsorption and desorption of five different macroporous adsorption resins, the static adsorption kinetics curve of NKA-Ⅱ resin, the maximum sample load, and the gradient elution were investigated. The UPLC-Q-TOF-MS/MS was employed for qualitative analysis of the newly-prepared total proanthocyanidins of C. axillaris pericarp. As revealed by the results, NKA-Ⅱ resin displayed strong adsorption and desorption toward total proanthocyanidins. The sample solution(50 mg·mL~(-1)) was prepared from 70% ethanol crude extract of C. axillaris pericarp dissolved in water and 7-fold BV of the sample solution was loaded, followed by static adsorption for 12 h. After 8-fold BV of distilled water and 6-fold BV of 10% ethanol were employed to remove impurities, the solution was eluted with 8-fold BV of 50% ethanol, concentrated, and dried under reduced pressure, and purified total proanthocyanidin powder was therefore obtained. Measured by vanillin-hydrochloric acid method, the purity and transfer rate of total proanthocyanidins were 47.67% and 59.92%, respectively, indicating the feasibi-lity of the optimized process. UPLC-Q-TOF-MS/MS qualitative analysis identified 16 procyanidins in C. axillaris total proanthocyanidins. The optimized purification process is simple in operation and accurate in component identification, and it can be applied to the process investigation of a class of components that are difficult to be separated and purified. It can also provide technical support and research ideas for the comprehensive utilization of industrial waste.

Linking anthocyanin diversity, hue, and genetics in purple corn.

While maize with anthocyanin-rich pericarp (purple corn) is rising in popularity as a source of natural colorant for foods and beverages, information on color range and stability-factors associated with anthocyanin decorations and compositional profiles-is currently limited. Furthermore, to maximize the scalability and meet growing demands, both anthocyanin concentrations and agronomic performance must improve in purple corn varieties. Using the natural anthocyanin diversity present in a purple corn landrace, Apache Red, we generated a population with variable flavonoid profiles-flavanol-anthocyanin condensed forms (0-83%), acylated anthocyanins (2-72%), pelargonidin-derived anthocyanins (5-99%), C-glycosyl flavone co-pigments up to 1904 µg/g, and with anthocyanin content up to 1598 µg/g. Each aspect of the flavonoid profiles was found to play a role in either the resulting extract hue or intensity. With genotyping-by-sequencing of this population, we mapped aspects of the flavonoid profile. Major quantitative trait loci (QTLs) for anthocyanin type were found near loci previously identified only in aleurone-pigmented maize varieties [Purple aleurone1 (Pr1) and Anthocyanin acyltransferase1 (Aat1)]. A QTL near P1 (Pericarp color1) was found for both flavone content and flavanol-anthocyanin condensed forms. A significant QTL associated with peonidin-derived anthocyanins near a candidate S-adenosylmethionine-dependent methyltransferase was also identified, warranting further investigation. Mapping total anthocyanin content produced signals near Aat1, the aleurone-associated bHLH R1 (Colored1), the plant color-associated MYB, Pl1 (Purple plant1), the aleurone-associated recessive intensifier, In1 (Intensifier1), and several previously unidentified candidates. This population represents one of the most anthocyanin diverse pericarp-pigmented maize varieties characterized to date. Moreover, the candidates identified here will serve as branching points for future research studying the genetic and molecular processes determining anthocyanin profile in pericarp.

Efficacy of Dipterocarpus alatus oil combination with Rhinacanthus nasutus leaf and Garcinia mangostana pericarps against canine demodicosis.

BACKGROUND AND AIM: Canine demodicosis is a skin disease that is a major global health problem in dogs. Ivermectin is a drug of choice for treatment, but it may cause toxicity in dogs carrying multidrug resistance mutation-1 gene mutations. Hence, alternative herbal medicines are used instead of the drug, such as Dipterocarpus alatus oil (YN oil), Rhinacanthus nasutus leaf (WC), and Garcinia mangostana pericarps (MG) extracts. This study aimed to determine the efficacy of D. alatus oil, R. nasutus leaf, and G. mangostana pericarp extracts on canine demodicosis in vivo. MATERIALS AND METHODS: Twenty-five mixed-breed dogs with localized demodicosis were examined. Dogs were diagnosed with demodicosis through deep skin scraping and screened with the inclusion criteria. Five dogs of each group were treated in five treatment groups (ivermectin, YN oil, YN oil+WC, YN oil+MG, and YN oil+WC+MG) for 1 month. The individual dogs were clinically evaluated, and the dermatological lesions were monitored daily for 60 days. RESULTS: Dermatological lesion improvement was predominantly observed in the group of dogs treated with YN oil+WC. This was evidenced by the disappearance of the hyperpigmentation and lichenification on day 28 post-treatment and alopecia on day 56 post-treatment. Moreover, no allergic or clinical signs were observed during treatment. CONCLUSION: YN oil+WC is an alternative herbal medicine that could be used for the treatment of localized canine demodicosis.

Purification and component identification of total proanthocyanidins in Choerospondias axillaris pericarp / 中国中药杂志

The present study determined the quantitative markers of total proanthocyanidins in the purification of the industrial waste Choerospondias axillaris pericarp based on the comparison results of high-performance liquid chromatography(HPLC) and mass spectrometry(MS) and optimized the purification process with two stable procyanidins as markers. The adsorption and desorption of five different macroporous adsorption resins, the static adsorption kinetics curve of NKA-Ⅱ resin, the maximum sample load, and the gradient elution were investigated. The UPLC-Q-TOF-MS/MS was employed for qualitative analysis of the newly-prepared total proanthocyanidins of C. axillaris pericarp. As revealed by the results, NKA-Ⅱ resin displayed strong adsorption and desorption toward total proanthocyanidins. The sample solution(50 mg·mL~(-1)) was prepared from 70% ethanol crude extract of C. axillaris pericarp dissolved in water and 7-fold BV of the sample solution was loaded, followed by static adsorption for 12 h. After 8-fold BV of distilled water and 6-fold BV of 10% ethanol were employed to remove impurities, the solution was eluted with 8-fold BV of 50% ethanol, concentrated, and dried under reduced pressure, and purified total proanthocyanidin powder was therefore obtained. Measured by vanillin-hydrochloric acid method, the purity and transfer rate of total proanthocyanidins were 47.67% and 59.92%, respectively, indicating the feasibi-lity of the optimized process. UPLC-Q-TOF-MS/MS qualitative analysis identified 16 procyanidins in C. axillaris total proanthocyanidins. The optimized purification process is simple in operation and accurate in component identification, and it can be applied to the process investigation of a class of components that are difficult to be separated and purified. It can also provide technical support and research ideas for the comprehensive utilization of industrial waste.

Evaluation of dynamic changes in the bioactive components in Citri Reticulatae Pericarpium (Citrus reticulata 'Chachi') under different harvesting and drying conditions.

BACKGROUND: The Citrus reticulata 'Chachi' pericarp (CRCP) is one cultivar of Citri Reticulatae Pericarpium (Chenpi), which is widely applied in medicine and food. To determine the potential value of CRCP harvested at different stages and subjected to different drying processes, the dynamic changes in the bioactive components were profiled and evaluated in this study. RESULTS: The contents of all non-volatile components, i.e. synephrine, limonin, phenolic acids and flavonoids, decreased with delayed harvest time. The volatiles thujene, α-pinene, ß-pinene, d-citronellol, d-citronellal, decanal, linalool, geraniol, l-cis-carveol, terpinen-4-ol, α-terpineol, carvacrol, perillaldehyde, methyl 2-(methylamino)benzoate and d-limonene were considered the characteristic components for distinguishing CRCP harvested at different stages. Phenolic acids, synephrine and limonin were stable at different drying temperatures; however, high-temperature drying at 60 °C induced a significant transformation in the flavonoids (especially polymethoxyflavones) and volatile substances in CRCP. CONCLUSIONS: The results suggested that most of the bioactive components declined with the growth of Citrus reticulata 'Chachi'. And it is believed that the fresh peel should be naturally sun-dried or dried at low temperature (30 or 45 °C) rather than at high temperature (60 °C) to prevent excessive loss of nutrients. © 2020 Society of Chemical Industry.

The Intestinal Efflux Transporter Inhibition Activity of Xanthones from Mangosteen Pericarp: An In Silico, In Vitro and Ex Vivo Approach.

The capacity of α-mangostin (α-MG) and ß-mangostin (ß-MG) from mangosteen pericarp on P-glycoprotein (Pgp) in silico, in vitro, and ex vivo was investigated in this study. Screening with the ADMET Predictor™ program predicted the two compounds to be both a Pgp inhibitor and Pgp substrate. The compounds tended to interact with Pgp and inhibit Pgp ATPase activity. Additionally, bidirectional transport on Caco-2 cell monolayers demonstrated a significantly lower efflux ratio than that of the control (α-(44.68) and ß-(46.08) MG versus the control (66.26); p < 0.05) indicating an inhibitory effect on Pgp activity. Test compounds additionally revealed a downregulation of MDR1 mRNA expression. Moreover, an ex vivo absorptive transport in everted mouse ileum confirmed the previous results that α-MG had a Pgp affinity inhibitor, leading to an increase in absorption of the Pgp substrate in the serosal side. In conclusion, α- and ß-MG have the capability to inhibit Pgp and they also alter Pgp expression, which makes them possible candidates for reducing multidrug resistance. Additionally, they influence the bioavailability and transport of Pgp substrate drugs.

Topological Interlocking and Geometric Stiffening as Complementary Strategies for Strong Plant Shells.

Many organisms encapsulate their embryos in hard, protective shells. While birds and reptiles largely rely on mineralized shells, plants often develop highly robust lignocellulosic shells. Despite the abundance of hard plant shells, particularly nutshells, it remains unclear which fundamental properties drive their mechanical stability. This multiscale analysis of six prominent (nut)shells (pine, pistachio, walnut, pecan, hazelnut, and macadamia) reveals geometric and structural strengthening mechanisms on the cellular and macroscopic length scales. The strongest tissues, found in walnut and pistachio, exploit the topological interlocking of 3D-puzzle cells and thereby outperform the fiber-reinforced structure of macadamia under tensile and compressive loading. On the macroscopic scale, strengthening occurs via an increased shell thickness, spherical shape, small size, and a lack of extended sutures. These functional interrelations suggest that simple geometric modifications are a powerful and resource-efficient strategy for plants to enhance the fracture resistance of entire shells and their tissues. Understanding the interplay between structure, geometry, and mechanics in hard plant shells provides new perspectives on the evolutionary diversification of hard seed coats, as well as insights for nutshell-based material applications.

Mangosteen Pericarp and Its Bioactive Xanthones: Potential Therapeutic Value in Alzheimer's Disease, Parkinson's Disease, and Depression with Pharmacokinetic and Safety Profiles.

Alzheimer's disease (AD), Parkinson's disease (PD), and depression are growing burdens for society globally, partly due to a lack of effective treatments. Mangosteen (Garcinia mangostana L.,) pericarp (MP) and its xanthones may provide therapeutic advantages for these disorders. In this review, we discuss potential therapeutic value of MP-derived agents in AD, PD, and depression with their pharmacokinetic and safety profiles. MP-derived agents have shown multifunctional effects including neuroprotective, antioxidant, and anti-neuroinflammatory actions. In addition, they target specific disease pathologies, such as amyloid beta production and deposition as well as cholinergic dysfunction in AD; α-synuclein aggregation in PD; and modulation of monoamine disturbance in depression. Particularly, the xanthone derivatives, including α-mangostin and γ-mangostin, exhibit potent pharmacological actions. However, low oral bioavailability and poor brain penetration may limit their therapeutic applications. These challenges can be overcome in part by administering as a form of MP extract (MPE) or using specific carrier systems. MPE and α-mangostin are generally safe and well-tolerated in animals. Furthermore, mangosteen-based products are safe for humans. Therefore, MPE and its bioactive xanthones are promising candidates for the treatment of AD, PD, and depression. Further studies including clinical trials are essential to decipher their efficacy, and pharmacokinetic and safety profiles in these disorders.

Acute and chronic oral toxicity assessment of longan sugar extracts derived from whole fruit and from fruit pulp in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Longan (Dimocarpus longan Lour.) is one of the most popular subtropical fruits. Various parts of longan, including seeds, pericarp and pulp, have long been used in traditional medicine in China, Thailand and other Asian countries. The pulp has high sugar, vitamin and mineral content as well as bioactive components. The seeds and pericarp have also been reported to contain beneficial polyphenolic compounds. Longan sugar extract from pulp (LGSP) is prepared as a conventional sugar product. Longan sugar extract from whole longan fruit (LGSW) is also offered as a health food and as a medicinal product. AIM OF THE STUDY: The objective of this study was to identify and compare potential health hazards of both LGSW and LGSP by testing for acute and chronic oral toxicity in rats. MATERIALS AND METHODS: In acute toxicity testing, an oral dose (20 g/kg) of either LGSW or LGSP was administered to groups of rats. Mortality and clinical signs of toxicity were observed for 24 h, and then daily for a total of 14 days. In the chronic toxicity test, either LGSW (1, 2.5 and 5 g/kg/day) or LGSP (5 g/kg/day) was administered orally for a period of 180 days. After that treatment period, the rats in the satellite groups which received the highest doses of either LGSW or LGSP were observed for an additional 28 days. The rats then underwent clinical observation, body and organ weight measurement, hematological and biochemical analyses, and histopathological examination. RESULTS: In the acute toxicity study, the oral administration of LGSP or LGSW in either pellet or syrup formulations did not cause mortality or any pathological abnormalities. In the chronic toxicity study, neither LGSW nor LGSP resulted in death or in any changes in behavior of the rats. All hematological and serum biochemical values of both the LGSW- and LGSP-treated groups were within the normal ranges. No histopathological abnormalities of any internal organs were observed. CONCLUSION: The safety of longan sugar extract made from whole fruit (pulp, seeds and pericarb) is comparable to that of longan sugar extract made from pulp alone.

Exposure to polyphenol-rich purple corn pericarp extract restricts fall armyworm (Spodoptera frugiperda) growth.

Bioactive compounds such as polyphenols in plants have been well studied for their potential insecticidal activities. These are considered as safe alternatives against chemical pesticides because of their lower persistence in environment, lower toxicity to humans and other organisms. However, they are present constitutively in lower amounts in plants and have to undergo complicated extraction methods - hampering their commercial exploitation in pest management. Using an inexpensive extraction method developed to recover polyphenol-rich liquid extract from purple corn pericarp, we recently documented that this extract has anti-feeding effects that cascade from larval to adult stages in a model herbivore tobacco hornworm (Manduca sexta). However, M. sexta does not feed on corn or any other major crops other than the species in the nightshade family (Solanaceae). In this study, we explored the same idea but using a generalist and common herbivore on corn, the fall armyworm (Spodoptera frugiperda). We found that purple corn pericarp extract inhibited the larval growth and development as well as negatively affected the pupal stages of S. frugiperda. However, unlike on M. sexta, time to complete larval life cycle was unaffected. Our findings confirm the toxicity of this extract on a generalist, economically important herbivore, but also suggest potential species-specific effects that should be explored further.

Distribution Patterns for Bioactive Constituents in Pericarp, Stalk and Seed of Forsythiae Fructus.

Forsythiae Fructus (FF) is a widely used folk medicine in China, Japan, and Korea. The distribution of bioactive constituents throughout the fruit segments has rarely been addressed, although mounting evidence suggests that plant secondary metabolites are synthesized and distributed regularly. The phytochemical profiles of three segments of FF (pericarp, stalk and seed) were firstly revealed by liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based quantitative analysis of twenty-one bioactive constituents, including three phenylethanoid glycosides, five lignans, eight flavonoids, and five phenolic acids to explore the spatial distribution of bioactive constituents. Furthermore, the hierarchical clustering analysis (HCA) and one-way analysis of variance (one-way ANOVA) were conducted to visualize and verify the distribution regularity of twenty-one analytes among three segments. The results showed that phytochemical profiles of the three segments were similar, i.e., phenylethanoid glycosides covering the most part were the predominant compounds, followed by lignans, flavonoids and phenolic acids. Nevertheless, the abundance of twenty-one bioactive constituents among three segments was different. Specifically, phenylethanoid glycosides were highly expressed in the seed; lignans were primarily enriched in the stalk; flavonoids were largely concentrated in the pericarp, while the contents of phenolic acids showed no much difference among various segments. The research improves our understanding of distribution patterns for bioactive constituents in FF, and also complements some scientific data for further exploring the quality formation mechanism of FF.