Homeopathic Formulations of Syzygium jambolanum Alleviate Glycation-Mediated Structural and Functional Modifications of Albumin: Evaluation through Multi-Spectroscopic and Microscopic Approaches.

BACKGROUND: The growing interest in identifying the mode of action of traditional medicines has strengthened its research. Syzygium jambolanum (Syzyg) is commonly prescribed in homeopathy and is a rich source of phytochemicals. OBJECTIVE: The present study aims to shed light on the anti-glycation molecular mechanism of Syzyg mother tincture (MT), 30c, and 200c on glycated human serum albumin (HSA) by multi-spectroscopic and microscopic approaches. METHODS: The phytochemicals and antioxidant potential of the Syzyg formulations were estimated by the high-performance liquid chromatography and spectroscopic technique, respectively. Glycation was initiated by incubating HSA with methylglyoxal, three Syzyg formulations, and the known inhibitor aminoguanidine in separate tubes at 37°C for 48 hours. The formation of glycation adducts was assessed by spectrofluorometer and affinity chromatography. The structural modifications were analyzed through circular dichroism, Fourier transform infrared spectroscopy, turbidity, 8-anilinonapthalene-1-sulfonic acid fluorescence, and nuclear magnetic resonance. Further, the formation of the aggregates was examined by thioflavin T, native-polyacrylamide gel electrophoresis, and transmission electron microscopy. Additionally, the functional modifications of glycated HSA were determined by esterase-like activity and antioxidant capacity. The binding analysis of Syzyg formulations with glycated HSA was evaluated by surface plasmon resonance (SPR). RESULTS: Syzyg formulations MT, 30c, and 200c contained gallic acid and ellagic acid as major phytochemicals, with concentrations of 16.02, 0.86, and 0.52 µg/mL, and 227.35, 1.35, and 0.84 µg/mL, respectively. Additionally, all three formulations had remarkable radical scavenging ability and could significantly inhibit glycation compared with aminoguanidine. Further, Syzyg formulations inhibited albumin's structural and functional modifications. SPR data showed that Syzyg formulations bind to glycated HSA with an equilibrium dissociation constant of 1.10 nM. CONCLUSION: Syzyg formulations inhibited the glycation process while maintaining the structural and functional integrity of HSA.

Development and Validation of Chromatographic Method for the Standardization of Homeopathic Formulation of Syzygium Cumini.

BACKGROUND: Syzygium cumini (Lam.), family Myrtaceae, has a long history of use in folk and traditional systems of indigenous medicine. Many homeopathic formulations of Jamun seeds are available in the market for their crucial usage as an anti-diabetic. Despite the popularity of homeopathic products, a lack of standard quality is a significant impediment in their acceptance. The present study aimed to develop and validate a chromatographic method for the standardization of the homeopathic formulation of Syzygium cumini. METHODS: The seeds of Syzygium cumini were studied for physicochemical evaluation and preliminary phytochemical screening. Also, the in-house standard and marketed homeopathic formulations of Syzigium cumini were standardized for pH, total fatty content, total phenolic and flavonoid content, with quantitative high-performance liquid chromatography- photodiode array detector (HPLC-PDA) analysis by using ellagic acid as a marker. RESULTS: The physicochemical characteristics of crude material were found to be within pharmacopeial limits. The phytochemical screening showed the presence of various secondary metabolites. The total phenolic and flavonoid content was higher in the in-house standard than in marketed formulations. A validated quantitative HPLC-PDA analysis showed variations of ellagic acid content in different homeopathic formulations. CONCLUSION: Physicochemical analysis and the HPLC method for quantitative estimation of ellagic acid can be used to standardize a homeopathic formulation of Syzygium cumini.

Syzygium jambolanum and Cephalandra indica homeopathic preparations inhibit albumin glycation and protect erythrocytes: an in vitro study.

BACKGROUND: Diabetes mellitus is a common endocrine disorder characterized by hyperglycemia eventually resulting in long-term complications. Increased glycation of proteins is implicated in the pathogenesis of complications. For treatment of diabetes, Syzygium jambolanum and Cephalandra indica are frequently prescribed in homeopathy. However their role in glycation is not well elucidated. The present study aimed to evaluate the role of these homeopathic preparations in glycation induced structural modifications and further to examine their cellular protection ability. METHODS: In human erythrocytes, in vitro mother tincture and dilutions of S. jambolanum (Sj ф, 30c, 200c), C. indica (Ci ф, 30c, 200c) and standard antiglycator (AG) were compared and their antiglycation potential assessed by the estimating different markers of glycation (frcutosamines, carbonyls, bound sugar), structural modifications (free amino and thiol group). Phytochemical characterization (total phenolic, flavonoids and glycosides contents) was performed. RESULTS: The homeopathic preparations have different mode of action on albumin glycation modifications. Sj ф preparation demonstrated effective inhibition of all glycation, structural modifications except amino group protection. When dilutions were compared, Sj preparations showed reduction of glycation, structural modifications. All preparations showed significant erythrocyte protection. Sj ф preparation exhibited noteworthy antiglycation and cell protection ability as compared to AG. CONCLUSION: These homeopathic preparations especially Sj ф prevented glycation induced albumin modifications and subsequent toxicity in human eryrthrocytre in vitro. Further investigation of their potential as antiglycators is justified.

Mechanistic role of Syzygium cumini (L.) Skeels in glycation induced diabetic nephropathy via RAGE-NF-κB pathway and extracellular proteins modifications: A molecular approach.

ETHNOPHARMACOLOGY RELEVANCE: Syzygium cumini (L.) Skeels (SC), an ancient medicinal plant, is used as a complementary and alternative medicine for treating diabetes mellitus and its associated complications, such as diabetic nephropathy (DN). Phytochemicals present in SC homeopathic formulations possess anti-glycemic, anti-glycation, anti-inflammatory, and antioxidant properties. Additionally, the non-enzymatic formation of advanced glycation end products (AGEs) increases during hyperglycemia in diabetes. AGEs interaction with their receptor of AGEs (RAGE) promotes inflammation via Nuclear Factor-κB (NF-κB) and the accumulation of Extracellular Matrix (ECM) proteins, contributing to the renal dysfunction in DN. However, the molecular mechanism through which SC formulations interact with the AGEs-RAGE-NF-κB pathway has not yet been investigated. AIM: This study aims to examine the impact of SC formulations on the RAGE-NF-κB pathway and ECM protein modifications in glycation-induced DN using a molecular approach. MATERIALS AND METHODS: Human serum albumin (10 mg/ml) was glycated with MGO (55 mM) in the presence of SC formulations - Mother tincture (MT), 30C, 200C for 7 days. Glycated samples were added to renal cells (HEK 293) for 24 h. Subsequently, cellular gene and protein expressions of RAGE, NF-κB, vascular endothelial growth factor (VEGF), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), collagen IV (Col IV), and fibronectin were determined using RT-qPCR and Western blot analysis. The immunofluorescence, luciferase assay, and chromatin immunoprecipitation techniques were employed to gain insights into glycation-induced NF-κB nuclear translocation, transcriptional activity, and its effect on RAGE promoter activity in SC-treated cells. RESULTS: SC formulations significantly downregulated glycation-induced elevated levels of RAGE and NF-κB. Mechanistically, SC formulations prevented NF-κB nuclear translocation, transcriptional activity, and RAGE promoter activity. Also, SC formulations significantly attenuated glycation-enhanced expressions of inflammatory cytokines (IL-6, TNF-α, and VEGF) and ECM proteins (Col IV and fibronectin). CONCLUSION: Our findings enlighten the molecular mechanism of SC in DN by targeting the AGEs-RAGE-NF-κB signaling pathway, inflammatory responses, and ECM accumulation. Hence, the study validates the protective role of SC formulations and signifies its novel potential for treating DN.

Effect of homeopathic preparations of Syzygium jambolanum and Cephalandra indica on gastrocnemius muscle of high fat and high fructose-induced type-2 diabetic rats.

BACKGROUND: Homeopathy is a holistic method of treatment that uses microdoses of natural substances originating from plants, minerals, or animal parts. Syzygium jambolanum and Cephalandra indica are used in homeopathy for treatment of type-2 diabetes. However, the molecular mechanisms responsible for such effects are not known. METHODS: Homeopathic preparations of S. jambolanum and C. indica in mother tincture, 6c and 30c were used to examine the molecular mechanism of antidiabetic effects in the skeletal muscle of rats with high fat and fructose-induced type-2 diabetes mellitus. After 30 days treatment, fasting blood glucose, serum insulin and insulin signaling molecules in the skeletal muscle (gastrocnemius) were measured. RESULTS: Diabetic rats showed a significant decrease in serum insulin and lipid profile as well as low levels of insulin receptor (IR), v-akt murine thymoma viral oncogene homolog (Akt), p-Akt(ser473) and glucose transporter-4 (GLUT4) protein expression (p < 0.05) with a significant increase in fasting blood glucose level (p < 0.05) compared to the control group. Treatment with homeopathic remedies significantly increased the serum insulin and expression of these proteins (p < 0.05) with a significant decrease in fasting blood glucose (p < 0.05) compared to diabetic rats. CONCLUSIONS: In the present study homeopathic preparations of S. jambolanum and C. indica, including ultramolecular dilutions exhibit antidiabetic effects, improving insulin action through activation of insulin signaling molecules in skeletal muscle of type-2 diabetic rats.

[Studies on the quality standard of xingnao tinctures].

OBJECTIVE: To establish the method for quality control of Xingnao tinctures. METHOD: The Mentholum, Flos Caryophylli and Borneoum Syntheticum in this medicine were identified by TLC method. The content of Mentholum was determined by GC. Conditions of GC were: With Naphthalene as an internal standard, packed glass column, Shimadzu 7G 2.1 mm x 3.2 m, carrier gas N2, flow rate 50 mL.min-1, column temperature. 145 degrees C, ingector and detector temperature. 180 degrees C, injection way of splitless and injection volume 3 microL. RESULT: The spots on TLC plates were clear, with no interference in the blank reference. The precision and repeatability of GC were are good respectively. The average recovery was 98.4%, RSD = 0.94%. CONCLUSION: This method was fast, simple, accurate and suitable for quality control of Xingnao tinctures.

Syzygium cumini (L.) skeels mitigate diabetic nephropathy by regulating Nrf2 pathway and mitocyhondrial dysfunction: In vitro and in vivo studies.

ETHNOPHARMACOLOGICAL PREVALENCE: Hyperglycemia in diabetes increases the generation of advanced glycation end products (AGEs) through non-enzymatic reactions. The interaction between AGEs and their receptors (RAGE) leads to oxidative and inflammatory stress, which plays a pivotal role in developing diabetic nephropathy. Syzygium cumini (SC) L. (DC.) homeopathic preparations viz. 200C, 30C, and mother tincture [MT] are used to treat diabetes. This study aimed to elucidate the regulatory effects of SC preparations (200C, 30C, and MT) on the nuclear factor erythroid 2-related factor 2 (Nrf2) - nuclear factor-κB (NF-κB) pathways and mitochondrial dysfunction in mitigating diabetic nephropathy (DN). MATERIALS AND METHODS: Streptozotocin-induced diabetic rats were treated with SC preparations (200C, 30C, MT; 1:20 dilution in distilled water; 600 µL/kg body weight) and metformin (45 mg/kg body weight) twice daily for 40 days. DN was evaluated through biochemical parameters and histological examination. Renal tissue lysates were analyzed for glycation markers. Protein and gene levels of Nrf2, NF-κB, and mitochondrial dysfunctional signaling were determined via western blotting and RT-qPCR. An immunohistochemical analysis of the kidneys was performed. In vitro, human serum albumin (HSA - 10 mg/ml) was glycated with methylglyoxal (MGO - 55 mM) in the presence of SC preparations (200C, 30C, MT) for eight days. Glycated samples (400 µg/mL) were incubated with renal cells (HEK-293) for 24 h. Further reactive oxygen species production, Nrf2 nuclear translocation, and protein or gene expression of Nrf2 and apoptosis markers were analyzed by western blotting, RT-qPCR, and flow cytometry. Molecular docking of gallic and ellagic acid with the HSA-MGO complex was performed. RESULT: In vivo experiments using streptozotocin-induced diabetic rats treated with SC preparations exhibited improved biochemical parameters, preserved kidney function, and reduced glycation adduct formation in a dose-dependent manner. Furthermore, SC preparations downregulated inflammatory mediators such as RAGE, NF-κB, vascular endothelial growth factor (VEGF), and Tumor necrosis factor α (TNF-α) while upregulating the Nrf2-dependent antioxidant and detoxification pathways. They downregulated B-cell lymphoma 2 (Bcl-2) associated X-protein (BAX), C/EBP homologous protein (CHOP), Dynamin-related protein 1 (DRP1), and upregulated BCL 2 gene expression. Notably, SC preparations facilitated nuclear translocation of Nrf2, leading to the upregulation of antioxidant enzymes and the downregulation of oxidative stress markers. Molecular docking studies revealed favorable interactions between gallic (-5.26 kcal/mol) and ellagic acid (-4.71 kcal/mol) with the HSA-MGO complex. CONCLUSION: SC preparations mitigate renal cell apoptosis and mitochondrial dysfunction through Nrf2-dependent mechanisms.

Syzygium jambolanum

A terapia com plantas medicinais vem sendo muito utilizada em váriaos países do mundo com um tratamento alternativo para doenças. O Syzygium jambolanum é amplament utilizado na medicina popular para o tratamento de diabetes, antidesentérico e no tratamento de afeçções das vias respiratórias. No Brasil é conhecido como jambolão. Devido aos altos custos com o tratamento do Diabetes a homeopatia deveria ser uma alternativa. (AU)

Diabetes y clínica homeopática / Diabetes and homeopathic clinic

Dentro de la terapéutica médica homeopática ortodoxa lo más importante es la individualidad del paciente, la totalidad de sus síntomas y la elección medicamentosa con base en ello. La diabetes mellitus es calificada por la medicina convencional como una patología de tipo irreversible; sin embargo, siguiendo los principios homeopáticos, para un tratamiento exitoso se debe de tomar en cuenta al enfermo o paciente, y no a la enfermedad o al padecimiento. Asimismo, desde el punto de vista homeopático se buscará el equilibrio integral de los pacientes al presentar un enfoque más amplio, así como una mirada centrada en el individuo enfermo en su conjunto sin perder la importancia del diagnóstico nosológico. Diversos autores han publicado terapéuticas con indicaciones características de algunos medicamentos homeopáticos para cuadros clínicos específicos; en este artículo se realiza una revisión de los más importantes, como Henry Clay Allen, León Vannier, James Tyler Kent, John Henry Clarke y Bernardo Vijnovsky, entre otros, con el fin de proporcionarle ai lector una gama de posibilidades que van de los síntomas orgánicos hasta los mentales, semejantes a los c1asificados dentro del diagnóstico de la diabetes mellitus.

For the orthodox homeopathic medical therapeutics the most important feature is the patient's individuality, aIl symptoms and the drug choice on this basis. Diabetes mellitus is skilled in traditional medicine as an irreversible type pathology, however, following homeopathic principles, in order to get a successful treatment we must to take into account the sick or patient and not the disease or condition. Also from the homeopathic scope, fuIl balance will be sought for patients to present a more comprehensive and focused look at the individual patient as a whole without losing the importance of nosological diagnosis. Several authors have reported therapeutic with indications characteristics of some homeopathic medicines for specific clinical conditions; this article carried out a review of the most important such as Henry Clay Allen, Leon Vannier, James Taylor Kent, John Henry Clarke and Bernardo Vijnovsky, among others, with the order to provide the reader with a range of possibilities based from organic to mental symptoms similar to those ranked in the diagnosis of diabetes mellitus.

Diabetes y clínica homeopática / Diabetes and homeopathic clinic

Dentro de la terapéutica médica homeopática ortodoxa lo más importante es la individualidad del paciente, la totalidad de sus síntomas y la elección medicamentosa con base en ello. La diabetes mellitus es calificada por la medicina convencional como una patología de tipo irreversible; sin embargo, siguiendo los principios homeopáticos, para un tratamiento exitoso se debe de tomar en cuenta al enfermo o paciente, y no a la enfermedad o al padecimiento. Asimismo, desde el punto de vista homeopático se buscará el equilibrio integral de los pacientes al presentar un enfoque más amplio, así como una mirada centrada en el individuo enfermo en su conjunto sin perder la importancia del diagnóstico nosológico. Diversos autores han publicado terapéuticas con indicaciones características de algunos medicamentos homeopáticos para cuadros clínicos específicos; en este artículo se realiza una revisión de los más importantes, como Henry Clay Allen, León Vannier, James Tyler Kent, John Henry Clarke y Bernardo Vijnovsky, entre otros, con el fin de proporcionarle ai lector una gama de posibilidades que van de los síntomas orgánicos hasta los mentales, semejantes a los c1asificados dentro del diagnóstico de la diabetes mellitus.

For the orthodox homeopathic medical therapeutics the most important feature is the patient's individuality, aIl symptoms and the drug choice on this basis. Diabetes mellitus is skilled in traditional medicine as an irreversible type pathology, however, following homeopathic principles, in order to get a successful treatment we must to take into account the sick or patient and not the disease or condition. Also from the homeopathic scope, fuIl balance will be sought for patients to present a more comprehensive and focused look at the individual patient as a whole without losing the importance of nosological diagnosis. Several authors have reported therapeutic with indications characteristics of some homeopathic medicines for specific clinical conditions; this article carried out a review of the most important such as Henry Clay Allen, Leon Vannier, James Taylor Kent, John Henry Clarke and Bernardo Vijnovsky, among others, with the order to provide the reader with a range of possibilities based from organic to mental symptoms similar to those ranked in the diagnosis of diabetes mellitus.

Tratamento para Diabetes melito tipo 1 canina através de medicamentos homeopáticos / Treatment for Diabetes mellitus type 1 canine with homeopathic medicine

A diabetes mellitus é uma doença crônica sistêmica decorrente de uma deficiência relativa ou absoluta de insulina. É uma das endocrinopatias mais comuns nos cães e pode ser fatal se não for diagnosticada e tratada adequadamente. É um conjunto de manifestações clínicas que afeta sereshumanos e animais: o fenômeno predisponente é o metabolismo anormal ou inadequado da glicose, em decorrência de uma deficiência relativa ou absoluta de insulina. É uma síndrome que compromete o metabolismo dos carboidratos, das gorduras, e das proteínas, devido a, deficiência parcial ou absoluta da secreção de insulina dada pelas células beta, produzidas pelas ilhotas de Langerhans, no pâncreas ou por redução da sensibilidade dos tecidos à insulina. O objetivo deste trabalho é revisar a literatura, os sinais clínicos, sintomas e complicações da diabetes mellitus tipo I canina e seu tratamento tradicional, e discutir a utilização de medicamentos homeopáticos. (AU)

Valoracion de medicamentos homeopaticos y alopaticos en el tratamiento de ratas con diabetes mellitus inducida por aloxana / Evaluation of homeopathic and allopathic drugs in the treatment of diabetes mellitus in rats induced by alloxan

La terapeutica homeopatica asi como la alopatica ofrecen medicamentos hipoglucemiantes con buenos efectos en el tratamiento de la diabetes mellitus. En el presente trabajo se realizo un estudio comparativo entre algunos medicamentos homeopaticos: (Syzigium, Uranium nitricum, Tronadora y Phosphorus) y medicamentos alopaticos (Biguanidas y Tolbutamida) para conocer sus resultados en el caso de diabetes inducida con Aloxana en ratas. Los resultados obtenidos permiten concluir que Syzigium y Uranium nitricum dieron buenos resultados como hipoglucemiantes; la Tolbutamida y la Tronadora dieron resultados inciertos; el Fosforo dio resultados buenos en una fase inicial, pero al final del estudio su efecto no fue seguro. Las Biguanidas manifestaron buenos resultados a lo largo de todo el experimento. Dado que los medicamentos probados aqui relatados, son de uso comun en terapia humana de Diabetes Mellitus, cabe la posibilidad de obtener buenos resultados clinicos, en las personas tratadas con dichos medicamentos, dejando abierta la investigacion para ampliar las conclusiones de acuerdo ;a los resultados que se sigan obteniendo en el futuro

Acción cardiovascular de extractos acuosos de hojas de Syzygium Jambos (L.) Alston / Cardiovascular action of aqueos extracts of leaf syzygium Jambolanum

En Costa Rica, existe una serie de plantas a las cuales se les atribuyen propiedades cardiovasculares. En este estudio se trató de demostrar el posible efecto hipotensor de extractos acuosos de hojas Syzygium Jambos (L.) Alston. Luego de algunas pruebas preliminares, la fracción acuosa del extracto de hojas tiernas heridas de S. Jambos, sometido a fraccionamientos con acetato de etilo, fue administrada intravenosamente a preparaciones caninas agudas, para efectuar los registros de presión arterial. Con el propósito de explorar variaciones en la resistencia vascular periférica, se utilizó la técnica denominada miembro posterior aislado de perro. La dosis mínima de 0,003 ml/kg produjo un descenso en la presión arterial media de 1,57 mmHg; con la dosis máxima utilizada (0,15 ml/kg), la disminución promedio fue de 55,07 mmHg. El efecto hipotensor estuvo acompañado de bradicardia. No se encontró efecto directo del extracto sobre la resistencia periférica. Los resultados indican que la fracción acuosa del extracto de hojas tiernas hervidas de S. Jambos, sometido a fraccionamiento con acetato de etilo, tiene un marcado efecto hipotensor

Utilizacao de extrato de botao floral de jambolao (Syzygium jambolanum) na excrecao renal de agua e eletrolitos em ratos / Utilization of jambolao flower extract (Syzygium jambolanum) in the diuresis and electrolites excretion in mices

Ratos albinos machos, variedade Wistar, foram submeti dos ao extrato de botao floral de jambolao atraves de sonda gastrica. Foi observado um incremento no volume urinario e nao houve alteracao significante na excrecao renal de ions Na+ e K+ nas diferentes concentracoes do extrato de jambolao

Valoracion de medicamentos homeopaticos y alopaticos en el tratamiento de ratas con diabetes mellitus inducida por aloxana / Evaluation of homeopathic and allopathic drugs in the treatment of diabetes mellitus in rats induced by alloxan

La terapeutica homeopatica asi como la alopatica ofrecen medicamentos hipoglucemiantes con buenos efectos en el tratamiento de la diabetes mellitus. En el presente trabajo se realizo un estudio comparativo entre algunos medicamentos homeopaticos: (Syzigium, Uranium nitricum, Tronadora y Phosphorus) y medicamentos alopaticos (Biguanidas y Tolbutamida) para conocer sus resultados en el caso de diabetes inducida con Aloxana en ratas. Los resultados obtenidos permiten concluir que Syzigium y Uranium nitricum dieron buenos resultados como hipoglucemiantes; la Tolbutamida y la Tronadora dieron resultados inciertos; el Fosforo dio resultados buenos en una fase inicial, pero al final del estudio su efecto no fue seguro. Las Biguanidas manifestaron buenos resultados a lo largo de todo el experimento. Dado que los medicamentos probados aqui relatados, son de uso comun en terapia humana de Diabetes Mellitus, cabe la posibilidad de obtener buenos resultados clinicos, en las personas tratadas con dichos medicamentos, dejando abierta la investigacion para ampliar las conclusiones de acuerdo ;a los resultados que se sigan obteniendo en el futuro

Efeitos antagonicos de plantas medicinais na diurese do rato / Antagonistic effects of medicinal plants in the diuresis of the mice

Os autores estudaram os efeitos da sobrecarga aquosa defolhas secas de jambolao e de casca seca de barbatimao, por via gastrica, na excrecao renal de agua, de sodio e de potassio do rato. Em relacao ao volume urinario observou-se uma diurese com o emprego do jambolao e uma antidiurese com o emprego do barbatimao, entretanto nao se observou alteracao na excrecao de sodio e de potassio, apos o emprego dos extratos das duas plantas

Efeitos do extrato de pericarpo de frutos maduros de jambolao (Syzygium jambolanum) na excrecao renal de agua e eletrolitos em ratos / Effects of the pericarp extract of jambolao (Syzygium jambolanum) mature fruits in the renal excretion of water and electrolites in mices

Changes in urinary volume and sodium and potassium excretion in rats submitted to jambolao mature fruit pericarp solution load. Male Wistar rats were submitted to a jambolao mature fruit pericarp solution load through a stomach cannula. It was observed a increased urinary volume and the sodium and potassium excretion showed similar values