Protective Effects of Zingerone Against Depression-Like Behavior and Biochemical Changes in Chronic Stressed Rats: Antioxidant Effects.

Ginger contains zingerone, an active constituent possessing antioxidant and neuroprotective properties. The present study was designed to explore the efficacy of the bioactive compound, zingerone, for treating behavioral and biochemical alterations in rats exposed to chronic restraint stress (CRS). Female Wistar rats were administered zingerone (25, 50, and 100 mg/kg p.o.) once daily for a period of 28 days while being exposed to CRS (6 h/day). Our results indicated that the stressed animals depicted depression-like behavior (reduced sucrose preference and increased immobility time) associated with increased lipid peroxidation (LPO) (cortex), decreased catalase (CAT) (hippocampus and cortex), and increased superoxide dismutase (SOD) (hippocampus and cortex). In addition, metabolic alterations were characterized by hyperglycemia and increased glycosylated hemoglobin in the CRS rats. However, no alterations were observed for learning and memory and in the levels of reduced glutathione. Repeated zingerone administration significantly reversed depression-like behavior elicited by CRS in rats. Furthermore, a significant antioxidant effect was exhibited by zingerone, as shown by decreased LPO and enhanced activity of SOD and CAT in chronically stressed rats. The findings of our study demonstrated that zingerone possesses protective actions against chronic stress-induced depressive-like behavioral, biochemical, and metabolic alterations and that its underlying mechanism may be attributed to its antioxidant properties. The results also signify its pharmacological and possible nutritional importance.

Adverse cutaneous toxicities by PD-1/PD-L1 immune checkpoint inhibitors: pathogenesis, treatment, and surveillance.

INTRODUCTION: The therapeutic use of humanised monoclonal programmed cell death 1 (PD-1) (pembrolizumab, and nivolumab) and programmed cell death ligand-1 (PD-L1) (atezolizumab, avelumab, durvalumab) immune checkpoint inhibitors (ICPi) as potent anticancer therapies is rapidly increasing. The mechanism of signalling of anti-PD-1/PD-L1 involves triggering cytotoxic CD4+/CD8 + T cell activation and subsequent abolition of cancer cells which induces specific immunologic adverse events that are specific to these therapies. These drugs can cause numerous cutaneous reactions and are characterized as the most frequent immune-related adverse events (irAEs). Majority of cutaneous irAEs range from non-specific eruptions to detectible skin manifestations, which may be self-limiting and present acceptable skin toxicity profiles, while some may produce life-threatening complications. OBJECTIVE: This review aims to illuminate the associated cutaneous irAEs related to drugs used in oncology along with the relevant mechanism(s) and management. AREAS COVERED: Literature was searched using various databases including Pub-Med, Google Scholar, and Medline. The search mainly involved research articles, retrospective studies, case reports, and clinicopathological findings. With this review article, an overview of the cutaneous irAEs with anti-PD-1/PD-L1 therapy, as well as suggestions, have been provided, so that their recognition at early stages could help in better management and would prevent treatment discontinuation.HIGHLIGHTSCutaneous adverse effects are the most prevalent immune-related adverse events induced by anti-PD-1/PD-L1 immune-checkpoint antibodies.Cutaneous toxicities mainly manifest in the form of maculopapular rash and pruritus.More specific cutaneous complications can also occur, including vitiligo, worsened psoriasis, lichenoid dermatitis, mucosal involvement (e.g. oral lichenoid reaction), dermatomyositis, lupus erythematosus.Cutaneous manifestations can be life-threatening including Stevens-Johnson syndrome/toxic epidermal necrolysis (TEN).Dermatologic toxicities are usually mild, readily manageable, and rarely result in significant morbidity.Adequate management of the cutaneous adverse event and recognition in early stages could lead to the prevention of worsening of the lesions and limit treatment disruption.

Advances in the pharmacotherapeutic management of post-traumatic stress disorder.

Introduction: Post-traumatic stress disorder (PTSD), a mental disorder, is associated with anxiety, depression, and social awkwardness resulting from past traumatic episodes like natural disasters, accidents, terrorist attacks, war, rape, and sexual violence. It affects primarily the amygdala, cortex, and hippocampus where neurochemical changes result in altered behavior. PTSD patients display impaired fear extinction, and past events keep haunting them. The topic presents relevant sections like PTSD pharmacotherapy, associated challenges, and the novel targets and drugs for future research and therapy.Areas covered: The authors discuss the current pharmacotherapy like SSRIs, NDRIs, SNRIs, anticonvulsants, antidepressants, and benzodiazepines, used to attenuate the associated symptoms. However, the primary focus being the novel and potential targets which can be explored better to understand possible future research and advanced therapy in PTSD. For the same, an account of both preclinical and clinical studies has been covered.Expert opinion: Excessive adverse effects, limited efficacy, and lower patient compliance are some of the major challenges with conventional drugs. Moreover, they correct only fewer symptoms without halting the disease progression. Several agents are investigated in different preclinical and clinical phases, which can potentially overcome the pitfalls and limitations associated with conventional therapies.

Protective effect of Indole-3-carbinol, an NF-κB inhibitor in experimental paradigm of Parkinson's disease: In silico and in vivo studies.

Parkinson's disease (PD) is a progressive neurodegenerative disorder, majorly with symptoms of motor dysfunction. Study was performed to explore the effect of nuclear factor κB (NF-κB) inhibitors against neurobehavioral abnormalities and neuroinflammation in PD. Cost effective in silico approaches of docking-based ligand -target complex predictions and optimal physicochemical properties were utilised to identify lead NF-κB inhibitor using database. Our studies revealed the potential hit Indole-3-carbinol (I3C) which was considered for the next phase, pharmacological validations. Intranigral administration of lipopolysaccharide (LPS) in rats is utilized as a neuroinflmmation model of PD. In the present study it caused an impairment in motor functions, its coordination, learning and memory as demonstrated in rotarod apparatus, beam balance test, open field test and Morris water maze test. Chronic administration of I3C for 21 days in intranigral LPS treated rats led to a significant improvement in motor functions, coordination, learning and memory which were associated with a decrease in the activity of inflammatory cytokines such as TNF-α and IL-6. Further, it was found to inhibit NF-κB whose levels increased after LPS administration. Moreover, decreased levels of malondialdehyde and increased levels of reduced glutathione, superoxide dismutase and catalase were observed in cortex and striatum after I3C administration in LPS rats. These results suggest a possible neuroprotective effect of I3C via amelioration of LPS-induced behavioural alterations, oxidative damage and neuroinflammation which in turn is attributed to its potent antioxidant and anti-inflammatory (NF-κB inhibition) property. The effect produced by I3C (50 mg/kg) was found to be comparable with levodopa-carbidopa combination (LD:CD) while, I3C (50 mg/kg) in combination with LD:CD exhibited a potentiating effect in improving motor impairments and cognitive deficit. The results thus depict I3C as a promising agent to delay neurodegeneration of the neurons in PD with improvement in motor functions and cognitive function.