2-Dodecyl-6-Methoxycyclohexa-2, 5-Diene-1, 4-Dione isolated from Averrhoa carambola L. root inhibits high glucose-induced EMT in HK-2 cells through targeting the regulation of miR-21-5p/Smad7 signaling pathway.

OBJECTIVE: 2-Dodecyl-6-Methoxycyclohexa-2, 5-Diene-1, 4-Dione (DMDD) isolated from Averrhoa carambola L. root, has been proven therapeutic effects on diabetic kidney disease (DKD). This research aims to assess DMDD's effects on DKD and to investigate its underlying mechanisms, to establish DMDD as a novel pharmaceutical agent for DKD treatment. METHODS: The human renal tubular epithelial (HK-2) cells were induced by high glucose (HG) to mimic DKD and followed by DMDD treatment. The cytotoxicity of DMDD was assessed using the Cell Counting Kit-8 (CCK-8) assay. The migratory capacity of HK-2 cells was evaluated through transwell and scratch-wound assays. To investigate the effect of Smad7 and miR-21-5p, lentiviral transfection was employed in HK-2 cells. Additionally, the expression of proteins related to epithelial-mesenchymal transition (EMT) and TGFß1/Smad2/3 pathway was checked by QRT-PCR, Western blot, and immunofluorescence techniques. RESULTS: This study has shown that DMDD significantly suppresses cell migration and the expression of Vimentin, α-SMA, TGFß1, and p-Smad2/3 in HK-2 cells under HG conditions. Concurrently, DMDD enhances the protein expression of E-cadherin and Smad7. Intriguingly, the therapeutic effect of DMDD was abrogated upon Smad7 silencing. Further investigations revealed that DMDD effectively inhibits miR-21-5p expression, which is upregulated by HG. Downregulation of miR-21-5p inhibits the activation of the TGFß1/Smad2/3 pathway and EMT induced by HG. In contrast, overexpression of miR-21-5p negates DMDD's therapeutic benefits. CONCLUSION: DMDD mitigates EMT in HG-induced HK-2 cells by modulating the miR-21-5p/Smad7 pathway, thereby inhibiting renal fibrosis in DKD. These findings suggest that DMDD holds promise as a potential therapeutic agent for DKD.

Sweet-type star fruit supplementation controls oxidative stress status and enhances the community walking capacity among elderly Thai.

BACKGROUND: Sweet-type Star fruit (SF) (Averrhoa carambola L.) is seasonal and more available for purchase in many markets in Thailand, when compared to the sour-type. But, its antioxidant activity results and potentially more modified supplement for elderly health during regular exercise in the community are unclear. OBJECTIVE: This study aimed to evaluate the antioxidant activity and physical capacity from supplementation of sweet-type SF among elderly people performing home walking exercise. METHODS: Mixing SF juice with honey industrially prepared the SF product. Its effects on oxidative stress status and physical capacity were studied in four groups; a supplement with walking exercise (n = 11, 67.00 ± 4.17 years), control (n = 12, aged 67.50 ± 5.58 years), supplementation (n = 11, aged 69.63 ± 7.14 years), and walking exercise (n = 12, aged 67.91 ± 4.33 years). Twenty grams or two teaspoons of supplement in warm water (150 mL) was the guideline for consumption twice daily for 4 weeks. In contrast, the walking exercise was prescribed with moderate intensity for 30 min, 3 days per week. Before and after the 4-week period, the oxidative stress status; glutathione (GSH), ascorbic acid (Vit C), total antioxidant capacity (TAC), and malondialdehyde (MDA), and 6-minute walking distance (6MWD) were evaluated. RESULTS: Results after the 4-week period, showed that Vit C and TAC increased and the MDA decreased significantly in the supplementation group, except the GSH and 6MWD results. The GSH and Vit C slightly decreased in the walking exercise group, whereas, its TAC, MDA and 6MWD increased significantly. Finally, The GSH and Vit C did not decrease and MDA slightly decreased in the combined group, but, their TAC and 6MWD increased significantly. CONCLUSION: Supplementation of the SF product during walking exercise possibly controls oxidative stress status and may enhance walking capacity.

Cytotoxic/antiproliferative and nutraceutical activity of aqueous and ethanolic extracts of green and mature Averrhoa carambola.

Averrhoa carambola L. presents in its composition diversity of nutrients and vitamins. The present study aimed to extract water and fat-soluble compounds from this fruit at different stages of maturation (green and mature), perform the physical-chemical characterization as well as evaluate its cytotoxicity against hepatoma cells of Rattus norvegicus (HTC). The physicochemical results showed that the pH and molar acidity is influenced by the fruit maturation state. The fruit presented high percentage of moisture, while the percentage of total minerals (ash) increased according to its maturation stage. The results of the phytochemical screening showed that star fruits present phenolic compounds. The antioxidant activity showed greater potential for the ethanolic extracts of the green and mature star fruit. For HTC cells treated with ethanolic extract of green and mature star fruit the data show absence of cytotoxic effect. The tests with the aqueous extract showed cytotoxic/antiproliferative effect of green and mature star fruit extract, in 24, 48 and 72 hours. The presence of nutraceutical compounds and the cytotoxic/antiproliferative activity were more expressive in the aqueous extract, being an option of easily accessible solvent economic and not harmful to organisms.

Averrhoa carambola L. fruit and stem metabolites profiling and immunostimulatory action mechanisms against cyclosporine induced toxic effects in rat model as analyzed using UHPLC/MS-MS-based chemometrics and bioassays.

The Averrhoa carambola L. tree encompasses a myriad of phytochemicals contributing to its nutritional and health benefits. The current study aims at investigating the A. carambola L. the metabolite profile grown in tropical and temperate regions represented by fruit and stem, for the first time using UPLC/MS-based molecular networking and chemometrics. Asides, assessment of the immunostimulatory effect of ripe fruit and stem, was compared in relation to metabolite fingerprints. Eighty metabolites were identified, 8 of which are first-time to be reported including 3 dihydrochalcone-C-glycosides, 4 flavonoids, and one phenolic. Multivariate data analysis revealed dihydrochalcones as origin-discriminating metabolites between temperate and tropical grown fruits. Further, an in vivo immunomodulatory assay in a cyclosporine A-induced rat model revealed a potential immune-enhancing effect as manifested by down-regulation of inflammatory markers (IL-6, INF-γ, IL-1, TLR4, and ESR) concurrent with the up-regulation of CD4 level and the CD4/CD8 ratio. Moreover, both extracts suppressed elevation of liver and kidney functions in serum as well as reduction in oxidative stress with concurrent increased levels of T-protein, albumin, globulin, and A/G ratio. This study pinpoints differences in secondary metabolite profiles amongst A. carambola L. accessions from different origins and organ type and its immunomodulatory action mechanisms.

Death associated with ingestion of starfruit (Averrhoa carambola) in a patient with chronic kidney disease.

We detail a case of a 74-year-old female with a history of chronic kidney disease (CKD) and diabetes mellitus (DM) who initially presented to the Emergency Department (ED) with intractable hiccups after ingesting two whole starfruit (SF) and quickly became critically ill while in the ED. Our patient was admitted and received several rounds of hemodialysis, but efforts proved futile, as the patient expired during her hospital course. To the best of our knowledge, this is the first fatality reported due to SF ingestion in the U.S, and highlights the need for both a better understanding of SF intoxication and clearer guidelines and timing for treatment. Due to the increased mortality of patients who consume SF with a medical history of CKD or DM, it is prudent that Emergency Physicians are familiar with the clinical presentation and management options for SF toxicity.

Averrhoa carambola L. fruit polyphenols ameliorate hyperlipidemia, hepatic steatosis, and hyperglycemia by modulating lipid and glucose metabolism in mice with obesity.

BACKGROUND: Hyperlipidemia, hepatic steatosis, and hyperglycemia are common metabolic complications of obesity. The objective of the present study is to investigate the in vivo protective effect of Averrhoa carambola L. fruit polyphenols (ACFP) on hyperlipidemia, hepatic steatosis, and hyperglycemia in mice with high-fat diet (HFD)-induced obesity and elucidate the mechanisms of action underlying the beneficial effects of ACFP. Thirty-six specific pathogen-free male C57BL/6J mice (4 weeks old, weighing 17.1-19.9 g) were randomly divided into three groups and fed with a low-fat diet (LFD, 10% fat energy), HFD (45% fat energy), or HFD supplemented with ACFP by intragastric administration for 14 weeks. Obesity-related biochemical indexes and hepatic gene expression levels were determined. The statistical analyses were conducted using one-way analysis of variance (ANOVA) followed by Duncan's multiple range test. RESULTS: The results showed that the body weight gain, serum triglycerides, total cholesterol, glucose, insulin resistance index, and steatosis grade in the ACFP group decreased by 29.57%, 26.25%, 27.4%, 19.6%, 40.32%, and 40%, respectively, compared to the HFD group. Gene expression analysis indicated that ACFP treatment improved the gene expression profiles involved in lipid and glucose metabolism compared to the HFD group. CONCLUSION: ACFP protected from HFD-induced obesity and obesity-associated hyperlipidemia, hepatic steatosis, and hyperglycemia by improving lipid and glucose metabolism in mice. © 2023 Society of Chemical Industry.

Evaluation of anti-quorum sensing potential of Averrhoa bilimbi (Kamias) against Pseudomonas aeruginosa ATCC 27853

BACKGROUND AND OBJECTIVE@#Many opportunistic and nosocomial pathogens like Pseudomonas aeruginosa are very reliant on a bacterium-to-bacterium communication system called quorum sensing (QS). Without the aforementioned process, gene expressions associated with virulence factors will not be produced. In this study, the sub-inhibitory concentrations (sub-MICs) of methanolic leaf extract and obtained fractions from Averrhoa bilimbi (kamias) were screened for ability to inhibit quorum sensing-controlled phenotypes of P. aeruginosa ATCC 27853.@*METHODOLOGY@#A. bilimbi crude extract was fractionated through liquid-liquid extraction, producing four (4) fractions: hexane fraction, dichloromethane (DCM) fraction, ethyl acetate (EtOAc) fraction, and water (H2O) fraction. Among the sub-MICs obtained from resazurin-based fluorimetric microtiter assay, only 50 μg/mL was utilized in evaluating the anti-QS properties of crude extract and fr@*RESULTS@# In the swarming motility assay, hexane fraction (9.39 mm ± 0.67) and DCM fraction (10.82 mm ± 0.95) displayed restriction in the treated P. aeruginosa ATCC 27853 swarms against the control (16.20 mm ± 2.55). In the anti-pyocyanin production assay, hexane fraction exhibited an inhibition of 42.66 % ± 12.94. TLC analysis and phytochemical screening revealed that hexane fraction contains steroids, terpenes, triterpenes, and glycolipids; and DCM fraction contains cardiac glycosides, triterpenoids, terpenes, triterpenes, steroids, alkaloids, and glycolipids.@*CONCLUSION@#Hexane and DCM fractions obtained from A. bilimbi significantly inhibited swarming of P. aeruginosa ATCC 27853 while none of the extracts were able to significantly inhibit pyocyanin formation of P. aeruginosa ATCC 27853.

Phytochemical Screening and Antibacterial Activities of Aqueous and Alcoholic Extracts of Averrhoa bilimbi Leaf against Bacteria Isolated from Oral Cavity.

Medicinal herbs have been used as traditional treatments for many pathogens and extracted bioactive compounds from medicinal plants with a suitable therapeutic index for the production of new drugs. Moreover, they are utilized to evaluate different concentrations of aqueous and alcoholic extracts of Averrhoa bilimbi leaves and antibiotics against bacteria isolated from the oral cavity. This study was conducted simultaneously at the Departments of Botany and Biology, Shatrah Hospital, Thi-Qar, Iraq, during March and August 2021. A. bilimbi leaf extracts were utilized in the plant component examination and the assessment of the antibacterial activity. The bacterial strain of Escherichia coli and Klebsiella pneumoniae was isolated from the oral cavity. To test the antibacterial impact of the extracts on bacteria, the agar well diffusion method was used. The phytochemical screening indicated the presence of Alkaloids, Flavonoids, Sapiens, Steroids, Tannins, Glycosides, and Carbohydrates, followed by the absence of Tannins in aqueous extract. Due to the A. bilimbi leaf aqueous and methanol extract against E. coli, areas of inhibition were found (0.20 cm and 0.19 cm) at the concentration of 100 mg/ml, respectively. However, there were no regions of inhibition of the K. pneumoniae trend for both extracts. The sensitivity of bacterial isolates of E. coli and K. pneumonia to antibiotics was also tested through Gentamicin, Amoxycillin, Azithromycin, Ciprofloxacin, Penicillin, and Polymyxin B, and the regions of inhibition appeared against E. coli (0.5cm, 0 cm, 0.34 cm, 0.45 cm, 0 cm, and 0.12 cm, respectively). Furthermore, the regions of inhibition appeared against K. pneumoniae (3 cm, 0.3 cm, 0.4 cm, 0.55 cm, 0 cm, 0.66 cm, respectively). The antibiotics showed a higher inhibition zone, compared to the aqueous and alcoholic extracts; however, further studies are required to be conducted to validate its reliability.

Micrograph analysis of morphological alteration and cellular damage of fruit rot fungal pathogens treated with Averrhoa bilimbi fruit and Garcinia mangostana pericarp ethanolic extracts.

The aim of this study is to assess the antifungal action of Averrhoa bilimbi fruit and Garcinia mangostana pericarp ethanolic extracts in altering the morphology and causing cellular damage of Fusarium oxysporum, Fusarium proliferatum, Colletotrichum gloeosporioides and Lasiodiplodia theobromae. The pathogens were cultured on media containing both extracts individually and carbendazim as positive control, whereas media alone as negative control. All samples were processed for microscopy observations using scanning (SEM) and transmission electron (TEM) microscopes. Observation via SEM showed significant alterations in the hyphae of F. oxysporum, F. proliferatum and C. gloeosporioides compared to the control in which the hyphae were in normal form. However, no significant alteration in hyphae had been observed in the treated plate compared to the control for L. theobromae. The development of calcium carbonate crystals was also observed abundantly in control compared to treated pathogens for F. oxysporum and F. proliferatum only. This indicated that the plant extracts can inhibit some metabolic processes in the pathogens too. Observations via TEM had been conducted for F. proliferatum and C. gloeosporioides, respectively. The results showed disintegration of cytoplasmic organelles and cell wall, intense vacuolization and lyses part of fungal cells. The plant extracts have equivalent or even greater effects compared to commercial fungicide carbendazim.

Anti-Obesity Evaluation of Averrhoa carambola L. Leaves and Assessment of Its Polyphenols as Potential α-Glucosidase Inhibitors.

Averrhoa carambola L. is reported for its anti-obese and anti-diabetic activities. The present study aimed to investigate its aqueous methanol leaf extract (CLL) in vivo anti-obese activity along with the isolation and identification of bioactive compounds and their in vitro α-glucosidase inhibition assessment. CLL improved all obesity complications and exhibited significant activity in an obese rat model. Fourteen compounds, including four flavone glycosides (1-4) and ten dihydrochalcone glycosides (5-12), were isolated and identified using spectroscopic techniques. New compounds identified in planta included (1) apigenin 6-C-(2-deoxy-ß-D-galactopyranoside)-7-O-ß-D-quinovopyranoside, (8) phloretin 3'-C-(2-O-(E)-cinnamoyl-3-O-ß-D-fucopyranosyl-4-O-acetyl)-ß-D-fucopyranosyl-6'-O-ß-D fucopyranosyl-(1/2)-α-L arabinofuranoside, (11a) phloretin3'-C-(2-O-(E)-p-coumaroyl-3-O-ß-D-fucosyl-4-O-acetyl)-ß-D-fucosyl-6'-O-(2-O-ß-D-fucosyl)-α-L-arabinofuranoside, (11b) phloretin3'-C-(2-O-(Z)-p-coumaroyl-3-O-ß-D-fucosyl-4-O-acetyl)-ß-D-fucosyl-6'-O-(2-O-ß-D-fucosyl)-α-L-arabinofuranoside. Carambolaside M (5), carambolaside Ia (6), carambolaside J (7), carambolaside I (9), carambolaside P (10a), carambolaside O (10b), and carambolaside Q (12), which are reported for the first time from A. carambola L. leaves, whereas luteolin 6-C-α-L-rhamnopyranosyl-(1-2)-ß-D-fucopyranoside (2), apigenin 6-C-ß-D-galactopyranoside (3), and apigenin 6-C-α-L-rhamnopyranosyl-(1-2)-ß-L-fucopyranoside (4) are isolated for the first time from Family. Oxalidaceae. In vitro α-glucosidase inhibitory activity revealed the potential efficacy of flavone glycosides, viz., 1, 2, 3, and 4 as antidiabetic agents. In contrast, dihydrochalcone glycosides (5-11) showed weak activity, except for compound 12, which showed relatively strong activity.

Acute and sub-chronic toxicological evaluation of Averrhoa carambola leaves in Sprague Dawley rats.

Averrhoa carambola is a species of tree native to tropical Southeast Asia. It possesses antioxidant and anti-hyperlipidemia effects and has traditionally been used to treat a variety of ailments. However, the presence of oxalic acid in its fruits might restrict its consumption by individuals suffering from kidney disease, and caramboxin can cause neurotoxicity. In this study, we evaluated the acute and sub-chronic toxicity of the methanolic extract of A. carambola leaves (MEAC) in male and female rats. In the acute study, female rats were given a single oral dose of 5000 mg/kg of MEAC and closely examined for distinct indications of toxic effects during the first 4 h, periodically for 48 h, and daily thereafter for 14 days. Rats of both sexes were employed in the sub-chronic investigation for the 28-day repeated dose oral toxicity study. Results of the acute study revealed the safety of MEAC up to a dose of 5000 mg/kg where the rats did not show changes or signs of toxicity. In the sub-chronic toxicity study, MEAC (250, 500, and 1000 mg/kg) administration did not affect the body weight, food, and water consumption, motor coordination, behavior, or mental alertness in the treated rats. In addition, no variations in hematological or biochemical markers were found in MEAC-treated rats. In conclusion, these findings pinpoint the safety of MEAC at doses up to 5000 mg/kg. The leaves of A. carambola could be safely consumed by people with kidney disease to treat other ailments.

Actinomycetospora soli sp. nov., isolated from the rhizosphere soil of Averrhoa carambola L.

A novel actinobacterium, designated strain SF1T, was isolated from the rhizosphere soil of a star fruit plant (Averrhoa carambola L.) collected from Bangkok, Thailand, and its taxonomic position was evaluated. The strain showed morphological, chemotaxonomic and phylogenetic characteristics consistent with its classification in the genus Actinomycetospora. Strain SF1T was an aerobic, Gram-stain-positive and non-motile actinobacterium. Growth occurred at 15-35 °C, at pH 4.0-12.0 and in the presence of 0-10 % (w/v) NaCl. The 16S rRNA gene sequence of strain SF1T showed the highest similarity to Actinomycetospora chiangmaiensis YIM 0006T (99.5 %), Actinomycetospora corticicola 014-5T (98.8 %) and Actinomycetospora endophytica A-T 8314T (98.8 %). The genome sequencing revealed a genome size of 6.52 Mbp and a DNA G+C content of 74.0 %. In addition, the average nucleotide identity values between strain SF1T and reference strains, A. chiangmaiensis DSM 45062T, A. corticicola DSM 45772T and A. endophytica TBRC 5722T, were found to be 86.1, 86.5 and 79.7 %, respectively, and the level of digital DNA-DNA hybridization between them were 32.4, 32.4 and 23.3 %, respectively. The whole-cell hydrolysates of strain SF1T contained meso-diaminopimelic acid as the diagnostic diamino acid, with arabinose, galactose, glucose and ribose as whole-cell sugars. The predominant menaquinone was MK-8(H4). Major cellular fatty acids were iso-C16 : 0 and a summed feature consisting of C16 : 1 ω6c/C16 : 1 ω7c. Characterization based on chemotaxonomic, phylogenetic, phenotypic and genomic evidence demonstrated that strain SF1T represents a novel species of the genus Actinomycetospora, for which the name Actinomycetospora soli sp. nov. is proposed. The type strain is strain SF1T (=TBRC 15166T= NBRC 115295T).

Phytochemical characterization, antioxidant potential and antimicrobial activity of Averrhoa carambola L. (Oxalidaceae) against multiresistant pathogens / Caracterização fitoquímica, potencial antioxidante e atividade antimicrobiana de Averrhoa carambola L. (Oxalidaceae) frente a patógenos multirresistentes

Abstract The objective of this work was to perform the phytochemical characterization, to determine total phenols, antioxidant (AAO%) and antimicrobial potential of the ethanolic extracts of carambola. The phytochemical study was carried out through a qualitative analysis of the chemical constituents and quantitative determination of the phenol content By the Folin-Ciocalteu test. Qualitative and quantitative antioxidant tests were performed using the DPPH method (2,2 diphenyl-1-picryl-hydrazila) and iron reduction (FRAP). The minimum inhibitory concentration (MIC) was determined by microdilution in 96-well plates. The presence of pyrogallic tannins, steroids and saponins has been identified. The highest total phenol content, quantified in the samples, was found in the stem bark (0.0866 mgEAG/g) and in the fruit (0.0734 mgEAG/g). In the antioxidant evaluation, the extracts of the green fruit bagasse (AAO% 71.9%,) and stem bark at 50 μg/mL (AAO% 94%) with CE50 23.7 μg/mL. Leaf extracts, stem bark, ripe fruit bagasse and green fruit bagasse presented MICs of 100 μg/mL against multiresistant pathogenic bacteria and fungi.

Resumo O objetivo desse trabalho foi realizar a caracterização fitoquímica, determinar fenóis totais, potencial antioxidante (AAO%) e antimicrobiano dos extratos etanólicos de carambola O estudo fitoquímico foi realizado por meio de análise qualitativa dos constituintes químicos e determinação quantitativa do teor de fenóis totais pelo teste de Folin-Ciocalteu. Os testes antioxidantes qualitativos e quantitativos foram realizados pelo método do DPPH (2,2 difenil-1- picril-hidrazila) e redução do ferro (FRAP). A concentração inibitória mínima (CIM) foi determinada por microdiluição em placas de 96 poços. Foi identificada a presença de taninos pirogálicos, esteroides e saponinas. O maior teor de fenóis totais, quantificado nas amostras, foi encontrado na casca do caule (0,0866 mg EAG/g) e no fruto (0,0734 mg EAG/g). Na avaliação antioxidante destacaram-se a 500 µg/mL os extratos do bagaço do fruto verde (AAO% 71,9%,), e casca do caule a 50 µg/mL (AAO% 94%) com CE50 23,7 µg/mL. Os extratos das folhas, casca do caule, bagaço do fruto maduro e bagaço do fruto verde apresentaram CIM de 100 µg/mL contra bactérias e fungos patogênicos multirresistentes.

Physicochemical Properties and Effects of Fruit Pulps from the Amazon Biome on Physiological Parameters in Rats.

This study aimed to analyze the physicochemical characteristics and the effects of Amazonian pulp fruits consumption, such as araçá-boi (Eugenia stipitata), abiu grande (Pouteria caimito), araticum (Annona crassiflora), biri-biri (Averrhoa bilimbi L.), and yellow mangosteen (Garcinia xanthochymus), on hematologic, metabolic, renal, and hepatic function parameters in Wistar rats (n = 10 rats/group). The pulp of abiu had the highest levels of soluble solids, sugars, and pH. Biri-biri pulp had the highest levels of ascorbic acid and total titratable acidity, and a low pH. The araticum pulp had higher (p ≤ 0.05) ash content, total phenolic compounds, and antioxidant activity than the pulp of other analyzed fruits. No significant increase in hematocrit, nor reduction of blood glucose, plasma cholesterol, and serum levels of glutamic-pyruvic transaminase (TGP), creatinine, and urea was observed in experimental groups relative to the control group of rats after the consumption of fruits pulp. The intake of abiu and araticum pulps promoted a significant reduction (p ≤ 0.05) in total leukocytes of the experimental groups as compared to the control group and only the intake of araticum significantly increased (p ≤ 0.05) triglyceride blood levels in rats (99.50 mg/dL). The regular consumption of biri-biri pulp for 30 days significantly (p ≤ 0.05) increased serum glutamic-oxaloacetic transaminase (TGO) levels in rats (116.83 U/L) compared to the control group (98.00 U/L). More researches are needed to generate knowledge about these promising Amazonian fruits, supporting the native fruit production, in addition to promoting health in the population and sustainability in the Amazon region.

Nephrotoxicity and neurotoxicity following star fruit (Averrhoa carambola) ingestion: a narrative review.

In recent times, star fruit (Averrhoa carambola) nephrotoxicity and neurotoxicity have been increasingly reported, both in individuals with pre-existing renal disease and those with previously normal renal function. We summarise the clinical findings of star fruit toxicity in humans and outline the important pathogenetic insights provided by animal studies. Google Scholar, EMBASE, Scopus and PubMed were searched from 1995 through July 2020 for case reports/series on renal or neurological manifestations of star fruit toxicity in humans and mechanisms of star fruit toxicity in animal studies. Ten case series and 28 case reports in humans (total number of individuals=136) were included and 8 animal studies were analysed. Ninety-four (69.1%) patients had prior renal impairment. Renal histology showed acute oxalate nephropathy with tubulointerstitial nephritis or tubular necrosis. Neurotoxicity manifestations ranged from hiccups to status epilepticus. Oxalate and caramboxin are considered the main substances causing nephrotoxicity and neurotoxicity. Caramboxin inhibits GABA binding and activates the glutamatergic receptors. Haemodialysis improved outcomes in neurotoxicity. Nephrotoxicity and neurotoxicity need to be looked for with star fruit toxicity, both in individuals with abnormal or normal renal function. Once star fruit intoxication is identified, early renal replacement therapy should be considered. Further studies on the mechanisms of star fruit toxicity are needed.

Acute Kidney Injury Following Star Fruit Ingestion: A Case Series.

Star fruit (Averrhoa carambola) is a popular fruit in many tropical countries, including Sri Lanka. It is rich in oxalic acid, which is nephrotoxic in higher concentrations. The development of both acute (AKI) and chronic kidney injury after oxalate nephropathy is often underrecognized. Here we discuss the risk factors, clinical features, treatment, and outcomes of 4 patients who developed AKI after star fruit ingestion. Baseline clinical characteristics, the amount of star fruit ingested, clinical presentation, investigation, and outcome of the patients (ages 28, 50, 54, and 55 y; all male) were traced. More common symptoms of acute star fruit intoxication were nausea, vomiting, and abdominal and back pain, followed by low urine output and high serum creatinine over hours to days. Urinary analysis of all patients demonstrated oxalate crystals. Histopathologic examination of renal tissues of all 4 patients revealed acute tubular damage with calcium oxalate crystals, interstitial edema, and inflammatory cellular infiltration. The presence of calcium oxalate crystals was further confirmed with the brilliant birefringence seen under polarized light. Two patients needed intermittent hemodialysis over a week owing to oliguria and uremia. The other 2 patients did not require hemodialysis and had improvement of renal function with supportive treatment. All had high renal function on discharge but were back to normal within a month. This study highlights AKI as a serious complication of star fruit ingestion. The type and quantity of star fruit ingested and some patient factors may play a role in the pathogenesis of AKI. Public education about this serious uncommon complication is important.

Rapid Structure-Based Annotation and Profiling of Dihydrochalcones in Star Fruit (Averrhoa carambola) Using UHPLC/Q-Orbitrap-MS and Molecular Networking.

Dihydrochalcones are a subclass of flavonoids. There has been growing interest in dihydrochalcones for their health benefits and potential to modulate flavor, but their comprehensive profile in diverse plant species is lacking. Star fruit is a tropical fruit rich in dihydrochalcones. In this study, a systematic annotation using UHPLC/Q-Orbitrap-MS and molecular networking was established to rapidly identify dihydrochalcones in 12 star fruit cultivars. A total of 53 dihydrochalcones were characterized within a short retention time including one novel compound (phloretin-3'-C-(2-O-trans-p-coumaroyl)-ß-d-fucopyranoside) and 23 compounds identified from the Averrhoa genus for the first time. 3-Hydroxyphloretin was the most abundant dihydrochalcone in star fruit. All the identified dihydrochalcones had a higher abundance in leaves compared to fruits. This is the first report that systematically investigates dihydrochalcones in star fruit of multiple cultivars, and the results could provide a useful reference for the future development and utilization of plant genetic resources.

Protective effect of 2-dodecyl-6-methoxycyclohexa-2, 5-diene-1, 4-dione, isolated from Averrhoa carambola L., against Aß1-42-induced apoptosis in SH-SY5Y cells by reversing Bcl-2/Bax ratio.

BACKGROUND AND PURPOSE: Aß1-42-induced neurotoxicity has been considered as a possible mechanism to aggravate the onset and progression of Alzheimer's disease (AD). In this study, we aim to determine the protective effect of DMDD on the apoptosis of SH-SY5Y cells induced by Aß1-42 and elucidate potential mechanism of DMDD's protective function in apoptosis. EXPERIMENTAL APPROACH: CCK-8, AnnexinV-FITC/PI flow cytometry, and transmission electron microscopy analysis were used to determine the protection of DMDD on Aß1-42-evoked apoptosis of SH-SY5Y cells. Cytochrome c release, JC-1 staining, and measuring the protein of Bcl-2 family by Western blot were applied to elucidate the mechanism of DMDD's protective function in apoptosis. KEY RESULTS: Three concentration of DMDD (5 µmol/L, 10 µmol/L, and 20 µmol/L) rescues the cell viability loss and apoptosis of SH-SY5Y cells cultivated in Aß1-42. The expressions of cleaved Caspase-3, -8, -9, the cytochrome c release, and mitochondrial membrane potential loss were inhibited by DMDD in Aß1-42-insulted SH-SY5Y cells. The Western blot analysis showed that DMDD pretreatment clearly downregulated the protein of Bax and upregulated Bcl-2. Moreover, the Bcl-2/Bax ratio was obviously decreased in cells only exposed to Aß1-42, but, which was suppressed by treated with DMDD. CONCLUSION AND IMPLICATIONS: DMDD attenuated the apoptosis of SH-SY5Y cells induced by Aß1-42 through reversing the Bcl-2/Bax ratio.

Phytochemical characterization, antioxidant potential and antimicrobial activity of Averrhoa carambola L. (Oxalidaceae) against multiresistant pathogens.

The objective of this work was to perform the phytochemical characterization, to determine total phenols, antioxidant (AAO%) and antimicrobial potential of the ethanolic extracts of carambola. The phytochemical study was carried out through a qualitative analysis of the chemical constituents and quantitative determination of the phenol content By the Folin-Ciocalteu test. Qualitative and quantitative antioxidant tests were performed using the DPPH method (2,2 diphenyl-1-picryl-hydrazila) and iron reduction (FRAP). The minimum inhibitory concentration (MIC) was determined by microdilution in 96-well plates. The presence of pyrogallic tannins, steroids and saponins has been identified. The highest total phenol content, quantified in the samples, was found in the stem bark (0.0866 mgEAG/g) and in the fruit (0.0734 mgEAG/g). In the antioxidant evaluation, the extracts of the green fruit bagasse (AAO% 71.9%,) and stem bark at 50 µg/mL (AAO% 94%) with CE50 23.7 µg/mL. Leaf extracts, stem bark, ripe fruit bagasse and green fruit bagasse presented MICs of 100 µg/mL against multiresistant pathogenic bacteria and fungi.

Acute nephrotoxicity and neurotoxicity associated with concentrated star fruit juice consumption.

Star fruit toxicity has been hugely described in patients with chronic kidney disease, either on conservative or renal replacement therapy. This is a case report of a man, without prior kidney or neurological dysfunction, who appeared to develop nephrotoxicity and neurotoxicity less than 12 hours after drinking concentrated star fruit juice (approximately 20 units of the fruit). He received timely renal replacement therapy and renal function fully recovered after discharge.