Potential utilization of ferulic acid and its derivatives in the management of metabolic diseases and disorders: An insight into mechanisms.

Metabolic diseases are abnormal conditions that impair the normal metabolic process, which involves converting food into energy at a cellular level, and cause difficulties like obesity and diabetes. The study aimed to investigate how ferulic acid (FA) and its derivatives could prevent different metabolic diseases and disorders and to understand the specific molecular mechanisms responsible for their therapeutic effects. Information regarding FA associations with metabolic diseases and disorders was compiled from different scientific search engines, including Science Direct, Wiley Online, PubMed, Scopus, Web of Science, Springer Link, and Google Scholar. This review revealed that FA exerts protective effects against metabolic diseases such as diabetes, diabetic retinopathy, neuropathy, nephropathy, cardiomyopathy, obesity, and diabetic hypertension, with beneficial effects on pancreatic cancer. Findings also indicated that FA improves insulin secretion by increasing Ca2+ influx through the L-type Ca2+ channel, thus aiding in diabetes management. Furthermore, FA regulates the activity of inflammatory cytokines (TNF-α, IL-18, and IL-1ß) and antioxidant enzymes (CAT, SOD, and GSH-Px) and reduces oxidative stress and inflammation, which are common features of metabolic diseases. FA also affects various signaling pathways, including the MAPK/NF-κB pathways, which play an important role in the progression of diabetic neuropathy and other metabolic disorders. Additionally, FA regulates apoptosis markers (Bcl-2, Bax, and caspase-3) and exerts its protective effects on cellular destruction. In conclusion, FA and its derivatives may act as potential medications for the management of metabolic diseases.

SIRT1/AMPK-mediated pathway: Ferulic acid from sugar beet pulp mitigating obesity-induced diabetes-linked complications and improving metabolic health.

Obesity-induced type 2 diabetes (T2D) increases the risk of metabolic syndrome due to the high calorie intake. The role of sugar beet pulp (SBP) in T2D and the mechanism of its action remain unclear, though it is abundant in phenolics and has antioxidant activity. In this study, we isolated and purified ferulic acid from SBP, referred to as SBP-E, and studied the underlying molecular mechanisms in the regulation of glucose and lipid metabolism developing high glucose/high fat diet-induced diabetic models in vitro and in vivo. SBP-E showed no cytotoxicity and reduced the oxidative stress by increasing glutathione (GSH) in human liver (HepG2) and rat skeletal muscle (L6) cells. It also decreased body weight gain, food intake, fasting blood glucose levels (FBGL), glucose intolerance, hepatic steatosis, and lipid accumulation. Additionally, SBP-E decreased the oxidative stress and improved the antioxidant enzyme levels in high-fat diet (HFD)-induced T2D mice. Further, SBP-E reduced plasma and liver advanced glycation end products (AGEs), malondialdehyde (MDA), and pro-inflammatory cytokines, and increased anti-inflammatory cytokines in HFD-fed mice. Importantly, SBP-E significantly elevated AMPK, glucose transporter, SIRT1 activity, and Nrf2 expression and decreased ACC activity and SREBP1 levels in diabetic models. Collectively, our study results suggest that SBP-E treatment can improve obesity-induced T2D by regulating glucose and lipid metabolism via SIRT1/AMPK signalling and the AMPK/SREBP1/ACC1 pathway.

Ferulic acid's therapeutic odyssey: nano formulations, pre-clinical investigations, and patent perspective.

INTRODUCTION: Ferulic acid (FA) is a phenolic phytochemical that has garnered the attention of the research community due to its abundant availability in nature. It is a compound that has been explored for its multifaceted therapeutic potential and benefits in modern and contemporary healthcare. AREAS COVERED: This review furnishes a compilation of the molecular mechanisms underlying the anti-diabetic, anticancer, antioxidant, and anti-inflammatory effects of FA. We also aim to excavate an in-depth analysis of the role of nanoformulations to achieve release control, reduce toxicity, and deliver FA at specified target sites. To corroborate the safety and efficacy of FA, a multitude of pre-clinical studies have also been conducted by researchers and have been discussed comprehensively in this review. The various patented innovations and newer paradigms pertaining to FA have also been presented. EXPERT OPINION: Enormous research has been conducted and should still be continued to find the best possible novel drug delivery system for FA delivery. The utilization of nanocarriers and nanoformulations has intrigued the scientists for delivery of FA, but before that, it is necessary to shed light upon toxicity, safety, and regulatory concerns of FA.

Mechanism of Ferulic Acid in PI3K/AKT Pathway and Research in Glioblastoma.

Phenolic acids and their analogues in nature exist in many diseases of oxidative stress with beneficial effects on human health (such as cancer). Phenolic acids possess a variety of pharmacological activities, with anti-inflammatory, anticancer and cytotoxic, antioxidant, immunomodulatory, antimicrobial, insecticidal and other biological activities. Numerous in vitro and in vivo studies have shown that because phenolic acids have antioxidant capacity, they can reflect their strong anticancer potential by regulating cell growth and metastasis and promoting cancer cell death. Studies have shown that the consumption of natural polyphenols can significantly reduce the risk of cancer metastasis. A combination of phenolic acids with traditional chemoradiation or other polyphenols may be effective in reducing cancer spread.Ferulic acid is ubiquitous, and widely found in plants, such as angelica, chuanxiong, cohote, three, edge, reed root, tomato, sweet corn, and rice are produced by the metabolism of phenylalanine and tyrosine. It is the most abundant hydroxyl cassia bark-acid acid in the plant kingdom, with anti-inflammatory, antidiabetic, anticancer and antioxidant activity, and polyphenols composed of hydroxyl cassia bark-acid derivatives, flavone-3-alcohol and flavonol retain non-cancer-cells-and-significantly-inhibit glioblastoma viability in a dose-dependent manner, which deserves further investigation as potential anticancer drugs. This paper summarizes the role of ferulic acid in the PI3K / AKT pathway and its mechanism in glioblastoma resistance.

Predictores de sobrevida en pacientes con hipertensión pulmonar primaria tratados con prostaciclina / Survival predictors in patients with primary pulmonary hypertension treated with prostacyclin

El tratamiento con prostaciclina en la hipertensión pulmonar primaria (HPP) se ha asociado a una disminución de la mortalidad, resultando en una alternativa terapéutica o como soporte previo al trasplante. Objetivo: determinar predictores clínicos o hemodinámicos de sobrevida en pacientes con HPP tratados con prostaciclina. Métodos: 57 pacientes consecutivos con diagnóstico de HPP evaluados en la Universidad de Alabama, período marzo 92-julio 97. Todos ellos tratados con infusión intravenosa continua de prostaciclína durante 19 meses (2-60), la dosis máxima fue 87 ñ 60 ng/kg/min. Para variables categóricas se utilizó test de Fisher y chi2, t test para variables continuas, y método de regresión logística para análisis multivariado. Se presentan los promedios ñ desviación standard p<0,05 fue considerado significativo. Resultados: edad 39 ñ 15 años, 48 pacientes sexo femenino, 41 pacientes en capacidad funcional IV (72 por ciento). Al final del seguimiento la capacidad funcional mejoró de 3,6 ñ 0, 4 a 3,16 ñ 0,7, p=0,0001, la fracción de eyeccíón ventricular derecha de 29 ñ 14 a 34:ñ 15 por ciento, p=0,0001, la presión sístólica de arteria pulmonar disminuyó de 86 ñ 20 mmHg a 76 ñ 23 mmHg, la resistencia vascular pulmonar de 1038 ñ 581 a 658 ñ 462 dinas/seg/cm-5, p=0,0001 con aumentos del índice cardíaco de 2,17 ñ 0,6 a 3,4 ñ 1,3 It/min/m2, p=0,006. La sobrevida fue de un 53 por ciento (n=30), 5 pacientes tuvieron doble trasplante pulmonar. En el análisis multivariado una capacidad funcional más deteriorada en la evaluación basal fue predictor independiente de mortalidad (OR=60, IC=3-1118), y la mejoría de la capacidad funcional predijo una mayor sobrevida (OR=0,21, IC=0,06-0,8). Estos hallazgos se correlacionaron con disminución de la presión sistólica de arteria pulmonar. Conclusión: nuestros resultados confirman la mejoría funcional y hemodinámica de los pacientes con HPP tratados con prostaciclína, sin embargo la mortalidad continúa siendo elevada. Una mejorcapacidad funcional al inicio de la terapia y una mejoría de ésta fueron asociadas a una mayor sobrevida. Pacientes con síntomas avanzados o refractarios debieran ser evaluados para trasplante