Search

Honokiol is a neolignan biphenol found in aerial parts of the Magnolia plant species. The Magnolia plant species traditionally belong to China and have been used for centuries to treat many pathological conditions. Honokiol mitigates the severity of several pathological conditions and has the potential to work as an anti-inflammatory, anti-angiogenic, anticancer, antioxidant, and neurotherapeutic agent. It has a long history of being employed in the healthcare practices of Southeast Asia, but in recent years, a greater scope of research has been conducted on it. Plenty of experimental evidence suggests it could be beneficial as a neuroprotective bioactive molecule. Honokiol has several pharmacological effects, leading to its exploration as a potential therapy for neurological diseases (NDs), including Alzheimer's disease (AD), Parkinson's disease (PD), cerebral ischemia, anxiety, depression, spinal cord injury, and so on. So, based on the previous experimentation reports, our goal is to discuss the neuroprotective properties of honokiol. Besides, honokiol derivatives have been highlighted recently as possible therapeutic options for NDs. So, this review focuses on honokiol's neurotherapeutic actions and toxicological profile to determine their safety and potential use in neurotherapeutics. [ABSTRACT FROM AUTHOR]

Introduction: The novel coronavirus infectious disease 2019 (COVID‐19) which is caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has emerged as a gigantic problem. The lung is the major target organ of SARS‐CoV‐2 and some of its variants like Delta and Omicron variant adapted in such a way that these variants can significantly damage this vital organ of the body. These variants raised a few eyebrows as the outbreaks have been seen in the vaccinated population. Patients develop severe respiratory illnesses which eventually prove fatal unless treated early. Main Body: Studies have shown that SARS‐CoV‐2 causes the release of pro‐inflammatory cytokines such as interleukin (IL)‐6, IL‐1β and tumor necrosis factor (TNF)‐α which are mediators of lung inflammation, lung damage, fever, and fibrosis. Additionally, various chemokines have been found to play an important role in the disease progression. A plethora of pro‐inflammatory cytokines "cytokine storm" has been observed in severe cases of SARS‐CoV‐2 infection leading to acute respiratory distress syndrome (ARDS) and pneumonia that may prove fatal. To counteract cytokine storm‐inducing lung inflammation, several promising immunomodulatory approaches are being investigated in numerous clinical trials. However, the benefits of using these strategies should outweigh the risks involved as the use of certain immunosuppressive approaches might lead the host susceptible to secondary bacterial infections. Conclusion: The present review discusses promising immunomodulatory approaches to manage lung inflammation in COVID‐19 cases which may serve as potential therapeutic options in the future and may prove lifesaving. Highlights: COVID‐19 mainly affects the lungs and in severe cases may lead to acute respiratory distress syndrome (ARDS) and pneumonia.Surprisingly, COVID‐19 can affect even the vaccinated population suggesting immune escape of the SARS‐CoV‐2 variants.Immunomodulatory approaches may modulate the immune response reducing lung inflammation and lessen the chances of an infected person developing ARDS or pneumonia.However, these approaches should be employed wisely based on the severity of the disease and where the benefits are greater than the risk involved. [ABSTRACT FROM AUTHOR]

The emergence of novel variants of SARS-CoV-2 and their abilities to evade the immune response elicited through presently available vaccination makes it essential to recognize the mechanisms through which SARS-CoV-2 interacts with the human immune response. It is essential not only to comprehend the infection mechanism of SARS-CoV-2 but also for the generation of effective and reliable vaccines against COVID-19. The effectiveness of the vaccine is supported by the adaptive immune response, which mainly consists of B and T cells, which play a critical role in deciding the prognosis of the COVID-19 disease. T cells are essential for reducing the viral load and containing the infection. A plethora of viral proteins can be recognized by T cells and provide a broad range of protection, especially amid the emergence of novel variants of SARS-CoV-2. However, the hyperactivation of the effector T cells and reduced number of lymphocytes have been found to be the key characteristics of the severe disease. Notably, excessive T cell activation may cause acute respiratory distress syndrome (ARDS) by producing unwarranted and excessive amounts of cytokines and chemokines. Nevertheless, it is still unknown how T-cell-mediated immune responses function in determining the prognosis of SARS-CoV-2 infection. Additionally, it is unknown how the functional perturbations in the T cells lead to the severe form of the disease and to reduced protection not only against SARS-CoV-2 but many other viral infections. Hence, an updated review has been developed to understand the involvement of T cells in the infection mechanism, which in turn determines the prognosis of the disease. Importantly, we have also focused on the T cells' exhaustion under certain conditions and how these functional perturbations can be modulated for an effective immune response against SARS-CoV-2. Additionally, a range of therapeutic strategies has been discussed that can elevate the T cell-mediated immune response either directly or indirectly. [ABSTRACT FROM AUTHOR]

Monkeypox virus is an orthopoxvirus sharing the common genus with variola and vaccinia virus. Most of the monkeypox (MPX) cases had been reported from the central and west African region (the main endemic areas) prior to 2022 but there was a sudden outbreak in May, 2022 disseminating the infections to thousands of people even in non-endemic countries, posing a global public health emergency. MPX was considered a rae and neglected disease, however the 2022 MPX outbreaks in multiple countries attracted attention of worldwide researchers to pace up for carrying out researches on various aspects of MPXV including attempts to design and develop diagnostics, vaccines, drugs and therapeutics counteract MPX. Apart from being a zoonotic disease, the current outbreaks highlighted rapid human-to-human transmission of MPXV, besides the reverse zoonosis has also been documented with recent first report of human-to-dog transmission, urging a call for the importance of one health approach. Atypical and unusual disease manifestations as well asymptomatic MPXV infections have also been observed during 2022 MPX outbreak. The affected patients typically develop a rash resulting in a mild disease followed by recovery with some supportive care and use of antivirals such as tecovirimat, cidofovir and brincidofovir in severe disease cases. Modified vaccinia Ankara (MVA) vaccine with an excellent safety profile has been recommended to patients with higher risk exposure and immunocompromised individuals. Moreover, another vaccine the replication-competent vaccine (ACAM2000) could be a suitable alternative to MVA's non-availability to some selective immunocompetent individuals. Current review highlights the salient aspects of management and treatment of monkeypox along with underlying promises in terms of therapeutics and a variety of challenges posed due to current global public health emergency situation to counteract MPX. [ABSTRACT FROM AUTHOR]

Cancer is one of the leading causes of death worldwide. Several treatments are available for cancer treatment, but many treatment methods are ineffective against multidrug-resistant cancer. Multidrug resistance (MDR) represents a major obstacle to effective therapeutic interventions against cancer. This review describes the known MDR mechanisms in cancer cells and discusses ongoing laboratory approaches and novel therapeutic strategies that aim to inhibit, circumvent, or reverse MDR development in various cancer types. In this review, we discuss both intrinsic and acquired drug resistance, in addition to highlighting hypoxia- and autophagy-mediated drug resistance mechanisms. Several factors, including individual genetic differences, such as mutations, altered epigenetics, enhanced drug efflux, cell death inhibition, and various other molecular and cellular mechanisms, are responsible for the development of resistance against anticancer agents. Drug resistance can also depend on cellular autophagic and hypoxic status. The expression of drug-resistant genes and the regulatory mechanisms that determine drug resistance are also discussed. Methods to circumvent MDR, including immunoprevention, the use of microparticles and nanomedicine might result in better strategies for fighting cancer. [ABSTRACT FROM AUTHOR]

Cancer is a fatal disorder that affects people across the globe, yet existing therapeutics are ineffective. The development of submicrometer transport for optimizing the biodistribution of systemically provided medications is the focus of nanomedicine. Nanoparticle- (NP-) based treatments may enable the development of novel therapeutic approaches to combat this deadly disorder. In multifunctional, multimodal imaging, and drug delivery carriers, NPs generally play a major role. They have emerged as potential strategies for the invention of innovative therapeutic procedures in the last decade. The exponential growth of nanotechnologies in recent years has increased public awareness of the application of these innovative therapeutic approaches. Many tumor-targeted nanomedicines have been studied in cancer therapy, and there is clear evidence for a significant improvement in the therapeutic index of antineoplastic drugs. Age-related factors such as metabolic and physiological alterations in old age and inadequate animal models are currently understudied in nanomedicine and pharmacology. This review highlighted the most important targeting approaches, as well as public awareness, therapeutic advancements, and future prospects in age-related metabolic variations, and tumor-targeted nanomedicine studies. [ABSTRACT FROM AUTHOR]

Cardiovascular diseases (CVDs) are a primary cause of death globally. A few classic and hybrid treatments exist to treat CVDs. However, they lack in both safety and effectiveness. Thus, innovative nanomaterials for disease diagnosis and treatment are urgently required. The tiny size of nanomaterials allows them to reach more areas of the heart and arteries, making them ideal for CVDs. Atherosclerosis causes arterial stenosis and reduced blood flow. The most common treatment is medication and surgery to stabilize the disease. Nanotechnologies are crucial in treating vascular disease. Nanomaterials may be able to deliver medications to lesion sites after being infused into the circulation. Newer point-of-care devices have also been considered together with nanomaterials. For example, this study will look at the use of nanomaterials in imaging, diagnosing, and treating CVDs. [ABSTRACT FROM AUTHOR]

Nuclear factor-κB (NF-κB) is a transcription factor that regulates various genes that mediate various cellular activities, including propagation, differentiation, motility, and survival. Abnormal activation of NF-κB is a common incidence in several cancers. Glioblastoma multiforme (GBM) is the most aggressive brain cancer described by high cellular heterogeneity and almost unavoidable relapse following surgery and resistance to traditional therapy. In GBM, NF-κB is abnormally activated by various stimuli. Its function has been associated with different processes, including regulation of cancer cells with stem-like phenotypes, invasion of cancer cells, and radiotherapy resistance identification of mesenchymal cells. Even though multimodal therapeutic approaches such as surgery, radiation therapy, and chemotherapeutic drugs are used for treating GBM, however; the estimated mortality rate for GBM patients is around 1 year. Therefore, it is necessary to find out new therapeutic approaches for treating GBM. Many studies are focusing on therapeutics having less adverse effects owing to the failure of conventional chemotherapy and targeted agents. Several studies of compounds suggested the involvement of NF-κB signaling pathways in the growth and development of a tumor and GBM cell apoptosis. In this review, we highlight the involvement of NF-κB signaling in the molecular understanding of GBM and natural compounds targeting NF-κB signaling. [ABSTRACT FROM AUTHOR]

Background: The objective of this study was to investigate the antinociceptive, anti-inflammatory, thrombolytic and hepatoprotective activities of root extracts of Premna esculenta (family: Verbenaceae). Methods: The analgesic activity was evaluated using the acetic-acid-induced writhing test in mice and radiant heat tail-flick method in rats. The anti-inflammatory activity was investigated by carrageenan-induced rat's paw edema, while the thrombolytic activity was evaluated by in vitro clot lysis model. The hepatoprotective activity was investigated against carbon-tetrachloride-induced liver damage in rats. Results: In acetic-acid-induced writhing test, chloroform and ethyl acetate fraction of ethanolic extract at a dose of 200 mg/kg showed a significant (p<0.001) reduction in the number of writhes with 85.96% and 61.98% of inhibition, respectively. In radiant heat tail-flick method, the ethanolic extract produced 88.49% (p<0.001) elongation of tail-flicking time at 90 min after oral administration at same dose level. In the carrageenan-induced edema test, the ethanolic extract at a dose of 200 mg/kg showed a significant inhibition of paw edema with 22.68% and 17.24% inhibition after the first and third hours of the study period, respectively. In clot lysis model, the ethanolic extract at 5 mg/mL induced a significant clot lysis activity (37.69%, p<0.001). Oral administration of ethanolic extract at the dose of 400 mg/kg/day for 7 days significantly (p<0.001) reduced the elevated levels of serum glutamic pyruvic transaminase, serum glutamyl oxaloacetate transaminase and alkaline phosphatase compared to the CCl4-treated control group. Conclusions: The results of the study demonstrated the antinociceptive, anti-inflammatory, thrombolytic and hepatoprotective activities of roots of P. esculenta. [ABSTRACT FROM AUTHOR]

Datura metel L. is an important medicinal plant of Solanaceae family which has extensive pharmacological properties. The present investigation was aimed to identify the presence of phytoconstituents and assess in vitro antibacterial, anti-biofilm, anti-diabetic, anti-inflammatory, antioxidant, cytotoxicity, and wound healing efficacy of D. metel leaves extract. Among different solvent extracts, methanolic extract showed higher amount of phenolic (124.61 ± 0.68 mg GAE/g), alkaloid (88.77 ± 1.01 mg AE/g), flavonoids (42.24 ± 0.18 mg QE/g), and tannins contents (38.72 ± 0.51 mg GAE/g). The extract exhibited not only significantly (P < 0.05) different antibacterial activities against pathogens tested but also showed maximum biofilm inhibition of 94, 88, and 92% against B. subtilis , MRSA, and E. coli , respectively. Anti-diabetic assay depicted 22.55 ± 0.62–79.41 ± 1.13% and 24.31 ± 1.47–72.59 ± 0.22% of α-amylase and α-glucosidase inhibition abilities of methanolic extract, respectively at varied concentrations. The methanolic extract showed potential anti-inflammatory effect (P < 0.05) by showing 28.11 ± 0.13, 34.94 ± 1.11, 55.73 ± 0.42, 73.28 ± 0.72, and 92.62 ± 1.33% of inhibition of protein denaturation at different concentrations with an IC 50 value of 52.45 µg/mL. The extract revealed significant (P < 0.05) rate of ABTS scavenging, DPPH degradation, and reducing power assay in a concentration dependent manner. The cytotoxicity assay was demonstrated on L929 mouse fibroblast cell line and found > 90% of cell viability in the presence of methanolic extract, thereby indicating its non-toxicity effect. Wound healing assay indicated that methanolic extract at 50 µg/mL closed 100% of wound gap after 24 h with high rate of migration and proliferation. Furthermore, GC–MS chromatogram revealed the presence of several components in methanolic extract, including neophytadiene, hexadecanoic acid, and hentriacontane as principal phytoconstituents. In conclusion, methanolic extract of D. metel leaves could be used as potent therapeutic agent not only for treating metabolic diseases but also superficial chronic diabetic wounds. [ABSTRACT FROM AUTHOR]

This research was carried out to investigate the thrombolytic effects of the methanolic extracts of five Bangladeshi plants. Phytochemical metabolites of those plants have been identified to elucidate whether the plant-derived metabolites are linked with the thrombolytic effects. Potential computer aided models were adopted in this study to find out a structure-function correlation between the phytochemical constituents and thrombolytic effects using the secondary metabolites as ligands and tissue plasminogen activator (t-PA) as receptor for the best fit ligand-receptor interaction. [ABSTRACT FROM AUTHOR]

This study was aimed to determine the potentialities of Pimpinella stewartii leaves extracts fractions towards the inhibition of acetylcholinesterase (AChE) activity as well as reduction of iron-induced lipid peroxidation in male Wistar rats (age – 50 days; weight – 280–300 g). Initially, animals were divided into 17 groups with 7 rats in each group. Gallic acid and quercetin were used as standards. The AChE activities of aqueous and ethanolic extract fractions of P. stewartii leaves were determined using standard protocol. Results showed that ethyl acetate extract fractions significantly (P = 0.01) inhibited the enzyme in a concentration dependent manner when compared to the aqueous extract fractions and the control group. Gallic acid and quercetin depicted higher inhibition of AChE activities than ethyl acetate extract fractions. Additionally, the IC 50 values for aqueous extract fractions, ethyl acetate extract fractions, gallic acid, and quercetin were estimated as 72.6 ± 2.72, 30.41 ± 0.56, 8.4 ± 0.22, and 6.82 ± 0.2 µg/mL, respectively. Furthermore, the lipid peroxidation activities of extracts fractions were assessed by estimating thiobarbituric acid reactive substances (TBARS) production. Both the extracts fractions showed significant protection against lipid peroxidation but the ethyl acetate extract fractions exhibited comparatively higher reductions in TBARS levels (P = 0.001). However, gallic acid and quercetin revealed higher reductions of pro-oxidants than the extracts fractions. In conclusion, findings of this study demonstrated pronounced AChE inhibitory activity and reduced lipid peroxidation trait of ethyl acetate extract fractions of P. stewartii leaves, and thus, suggested its paramount role as therapeutics against Alzheimer disease. [ABSTRACT FROM AUTHOR]

Globally, Alzheimer's disease (AD) is one of the most prevalent age-related neurodegenerative disorders associated with cognitive decline and memory deficits due to beta-amyloid deposition (Aβ) and tau protein hyperphosphorylation. To date, approximately 47 million people worldwide have AD. This figure will rise to an estimated 75.6 million by 2030 and 135.5 million by 2050. According to the literature, the efficacy of conventional medications for AD is statistically substantial, but clinical relevance is restricted to disease slowing rather than reversal. Withaferin A (WA) is a steroidal lactone glycowithanolides, a secondary metabolite with comprehensive biological effects. Biosynthetically, it is derived from Withania somnifera (Ashwagandha) and Acnistus breviflorus (Gallinero) through the mevalonate and non-mevalonate pathways. Mounting evidence shows that WA possesses inhibitory activities against developing a pathological marker of Alzheimer's diseases. Several cellular and animal models' particulates to AD have been conducted to assess the underlying protective effect of WA. In AD, the neuroprotective potential of WA is mediated by reduction of beta-amyloid plaque aggregation, tau protein accumulation, regulation of heat shock proteins, and inhibition of oxidative and inflammatory constituents. Despite the various preclinical studies on WA's therapeutic potentiality, less is known regarding its definite efficacy in humans for AD. Accordingly, the present study focuses on the biosynthesis of WA, the epidemiology and pathophysiology of AD, and finally the therapeutic potential of WA for the treatment and prevention of AD, highlighting the research and augmentation of new therapeutic approaches. Further clinical trials are necessary for evaluating the safety profile and confirming WA's neuroprotective potency against AD. [ABSTRACT FROM AUTHOR]

In recent years, the emergence of newly identified acute and chronic infectious disorders caused by diverse combinations of pathogens, termed polymicrobial diseases, has had catastrophic consequences for humans. Antimicrobial agents have been clinically proven to be effective in the pharmacological treatment of polymicrobial diseases. Unfortunately, an increasing trend in the emergence of multi-drug-resistant pathogens and limited options for delivery of antimicrobial drugs might seriously impact humans' efforts to combat polymicrobial diseases in the coming decades. New antimicrobial agents with novel mechanism(s) of action and new pharmaceutical formulations or delivery systems to target infected sites are urgently required. In this review, we discuss the prospective use of novel antimicrobial compounds isolated from natural products to treat polymicrobial infections, mainly via mechanisms related to inhibition of biofilm formation. Drug-delivery systems developed to deliver antimicrobial compounds to both intracellular and extracellular pathogens are discussed. We further discuss the effectiveness of several biofilm-targeted delivery strategies to eliminate polymicrobial biofilms. At the end, we review the applications and promising opportunities for various drug-delivery systems, when compared to conventional antimicrobial therapy, as a pharmacological means to treat polymicrobial diseases. [ABSTRACT FROM AUTHOR]

• Cytokines consist of large protein families such as interleukins, lymphokines, chemokines, interferons and involve in the regulation of the immune response such as immunotolerant activity through complex signaling pathways. • Several cytokines (IL-2, IL-11, G-CSF, GM-CSF, IFN-α, IFN-β, IFN-γ, etc.) are already approved as disease therapeutics, and many other cytokines are being investigated for their anti-cancer, anti-microbial, immunomodulatory properties in the preclinical studies and trials. • Interleukins, interferons, and other cytokines are potential immunoadjuvants as they can influence the development of antigen-specific responses when applied with a vaccine as an adjuvant. • Various properties of cytokines make them potential candidates for using them as therapeutic agents or vaccine adjuvant against both microbial diseases and cancer despite having some limitations. Cytokines are a protein family comprising interleukins, lymphokines, chemokines, monokines and interferons. They are significant constituents of the immune system, and they act in accordance with specific cytokine inhibiting compounds and receptors for the regulation of immune responses. Cytokine studies have resulted in the establishment of newer therapies which are being utilized for the treatment of several malignant diseases. The advancement of these therapies has occurred from two distinct strategies. The first strategy involves administrating the recombinant and purified cytokines, and the second strategy involves administrating the therapeutics which inhibits harmful effects of endogenous and overexpressed cytokines. Colony stimulating factors and interferons are two exemplary therapeutics of cytokines. An important effect of cytokine receptor antagonist is that they can serve as anti-inflammatory agents by altering the treatments of inflammation disorder, therefore inhibiting the effects of tumour necrosis factor. In this article, we have highlighted the research behind the establishment of cytokines as therapeutics and vaccine adjuvants, their role of immunotolerance, and their limitations. [ABSTRACT FROM AUTHOR]