Coronavirus disease 2019 (COVID-19) caused a severe epidemic due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Recent studies have found that patients do not completely recover from acute infections, but instead, suffer from a variety of post-acute sequelae of SARS-CoV-2 infection, known as long COVID. The effects of long COVID can be far-reaching, with a duration of up to six months and a range of symptoms such as cognitive dysfunction, immune dysregulation, microbiota dysbiosis, myalgic encephalomyelitis/chronic fatigue syndrome, myocarditis, pulmonary fibrosis, cough, diabetes, pain, reproductive dysfunction, and thrombus formation. However, recent studies have shown that naringenin and naringin have palliative effects on various COVID-19 sequelae. Flavonoids such as naringin and naringenin, commonly found in fruits and vegetables, have various positive effects, including reducing inflammation, preventing viral infections, and providing antioxidants. This article discusses the molecular mechanisms and clinical effects of naringin and naringenin on treating the above diseases. It proposes them as potential drugs for the treatment of long COVID, and it can be inferred that naringin and naringenin exhibit potential as extended long COVID medications, in the future likely serving as nutraceuticals or clinical supplements for the comprehensive alleviation of the various manifestations of COVID-19 complications.

This review describes the various innovative approaches implemented for naringin extraction as well as the recent developments in the field. Naringin was assessed in terms of its structure, chemical composition, and potential food sources. How naringin works pharmacologically was discussed, including its potential as an anti-diabetic, anti-inflammatory, and hepatoprotective substance. Citrus flavonoids are crucial herbal additives that have a huge spectrum of organic activities. Naringin is a nutritional flavanone glycoside that has been shown to be effective in the treatment of a few chronic disorders associated with ageing. Citrus fruits contain a common flavone glycoside that has specific pharmacological and biological properties. Naringin, a flavone glycoside with a range of intriguing characteristics, is abundant in citrus fruits. Naringin has been shown to have a variety of biological, medicinal, and pharmacological effects. Naringin is hydrolyzed into rhamnose and prunin by the naringinase, which also possesses l-rhamnosidase activity. D-glucosidase subsequently catalyzes the hydrolysis of prunin into glucose and naringenin. Naringin is known for having anti-inflammatory, antioxidant, and tumor-fighting effects. Numerous test animals and cell lines have been used to correlate naringin exposure to asthma, hyperlipidemia, diabetes, cancer, hyperthyroidism, and osteoporosis. This study focused on the many documented actions of naringin in in-vitro and in-vivo experimental and preclinical investigations, as well as its prospective therapeutic advantages, utilizing the information that is presently accessible in the literature. In addition to its pharmacokinetic characteristics, naringin\'s structure, distribution, different extraction methods, and potential use in the cosmetic, food, pharmaceutical, and animal feed sectors were discussed.

Neurodegenerative disorders (NDs) are a group of progressive, chronic, and disabling disorders that are highly prevalent and the incidence is on a constant rise globally. Alzheimer\'s disease (AD), one of the most common neurodegenerative disorders is hallmarked by cognitive impairment, amyloid-β (Aβ) deposition, hyperphosphorylation of tau protein, cholinergic dysfunction, mitochondrial toxicity, and neurodegeneration. Available therapeutic agents only provide symptomatic relief and their use are limited due to serious side effects. Recent research has recognized flavonoids as potential multi-target biomolecules that can reduce the pathogenesis of AD. Naringin, a natural citrus flavonoid has been traditionally used to treat various NDs including AD, and has gained special attention because exhibits a neuroprotective effect by affecting numerous signaling pathways with minimum adverse effects. Naringin reduces deposition of Aβ, hyperphosphorylation of tau protein, cholinergic dysfunction, oxidative stress burden, mitochondrial toxicity, the activity of glutamate receptors, and apoptosis of the neuronal cells. Additionally, it reduces the expression of phosphorylated-P38/P38 and the NF-κB signaling pathway, showing that a wide range of molecular targets is involved in naringin\'s neuroprotective action. The present study describes the possible pharmacological targets, signaling pathways, and molecular mechanisms of naringin involved in neuroprotection against AD-like pathology. Based on the above pre-clinical reports it can be concluded that naringin could be an alternative therapeutic agent for the management of AD-like manifestation. Thus, there is a strong recommendation to perform more preclinical and clinical studies to develop naringin as a novel molecule that could be a multi-target drug to counteract AD.

Naringin is the main component of Drynaria. Modern pharmacological studies have shown that naringin has a wide range of pharmacological activities, including antioxidant, anti-inflammatory, anti-apoptotic, anti-ulcer, and anti-osteoporosis effects. Its therapeutic effects have been observed in various clinical models, such as atherosclerosis, cardiovascular diseases, diabetes, neurodegenerative diseases, and rheumatic diseases. This review investigates the pharmacological effects of naringin and the associated mechanisms in improving flap survival. This review will also provide a reference for future rational application of naringin, especially in research to improve flap survival.

UNASSIGNED: The kidney is well-known as the vital organ which is responsible for maintaining body homeostasis and secretion of toxic metabolites. Renal injury is accompanied by oxidative stress which results in cellular apoptosis, lipid peroxidation, and reduction of antioxidant levels. Plant extracts and their phytoconstituents, owing to free radical scavenging properties, seem to be valuable against modern synthetic and chemical drugs. Naringin is a flavonoid present in citrus fruits with pharmacologic effects including antioxidant, anti-inflammatory, and anti-apoptotic properties. This review summarizes the renoprotective effects of naringin and discusses mechanisms of its action against renal injury.
UNASSIGNED: For this paper, original subject-related articles published up to October 2020 have been reviewed in the databases, including PubMed, Scopus, and Web of Science, and Google Scholar.
UNASSIGNED: Naringin increases antioxidant enzyme activity, and glutathione content, reduces lipid peroxidation and inhibits inflammatory cytokines. In the molecular investigation, naringin activates the Nrf-2 signaling, prevents apoptosis signaling, and inhibits the autophagy pathway. Besides, naringin could protect the kidney through modulating microRNA-10a in the kidney tissue in an acute kidney injury model.
UNASSIGNED: This review recommends that naringin can be considered a promising candidate to treat kidney dysfunction induced by oxidative stress in the future.

Naringin is a flavonoid found primarily in citrus species with especially high concentrations being present in grapefruit (Citrus paradisi), bitter orange (Citrus aurantium), and pomelo (Citrus grandis). Because of its many positive effects on human health, naringin has been the focus of increasing attention in recent years. Recently, conventional extraction methods have been commonly replaced with unconventional methods, such as ultrasound-assisted extraction (UAE) and other, more eco-friendly extraction methods requiring little-to-no environmentally harmful solvents or significantly less energy. Naringin analysis is most commonly done via high-performance liquid chromatography (HPLC), and ultrahigh-performance liquid chromatography (UHPLC) coupled with a mass spectrometer (MS) or a photodiode array (DAD) detector. The aim of this review is to provide an overview of recent trends developments in the extraction, sample preparation, and liquid chromatographic analysis of the compound originating from citrus fruits or their products.

Osteoporosis is a systemic bone disease characterized by decreased bone mass and quality and bone micro‑architecture degradation. Its primary cause is disorder of bone metabolism: Over‑formation of osteoclasts, resulting in increased bone resorption and insufficient osteogenesis. Traditional herbal flavonoids can be used as alternative drugs to prevent and treat osteoporosis due to their wide range of sources, structural diversity and less adverse effects. The present paper reviewed six flavonoids, including quercetin, icariin, hesperitin, naringin, chrysin and pueraria, that promote bone formation and have been widely studied in the literature over the past five years, with the aim of providing novel ideas for the development of drugs for bone‑associated disease.

Though the incidence of several cancers in Western societies is regulated wisely, some cancers such as breast, lung, and colorectal cancer are currently rising in many low- and middle-income countries due to increased risk factors triggered by societal and development problems. Surgery, chemotherapy, hormone, radiation, and targeted therapies are examples of traditional cancer treatment approaches. However, multiple short- and long-term adverse effects may also significantly affect patient prognosis depending on treatment-associated clinical factors. More and more research has been carried out to find new therapeutic agents in natural products, among which the bioactive compounds derived from plants have been increasingly studied. Naringin and naringenin are abundantly found in citrus fruits, such as oranges and grapefruits. A variety of cell signaling pathways mediates their anti-carcinogenic properties. Naringin and naringenin were also documented to overcome multidrug resistance, one of the major challenges to clinical practice due to multiple defense mechanisms in cancer. The effective parameters underlying the anticancer effects of naringenin and naringin include GSK3β inactivation, suppression of the gene and protein activation of NF-kB and COX-2, JAK2/STAT3 downregulation, downregulation of intracellular adhesion molecules-1, upregulation of Notch1 and tyrocite-specific genes, and activation of p38/MAPK and caspase-3. Thus, this review outlines the potential of naringin and naringenin in managing different types of cancers.

The cardioprotective role of naringin has been scientifically well demonstrated in various experimental models such as diabetic cardiomyopathy, ischemic heart diseases, diet-induced cardiac injury, antihypertensive and anti-platelet activities through various mechanisms. However, there is no meta-analysis performed on the cardioprotective activity of naringin. This systematic review and meta-analysis were focused to summarize and conclude the therapeutic benefits of naringin in various cardiovascular disorders using pre-clinical evidence. The online search was performed using electronic databases such as PubMed/Medline, Scopus, ScienceDirect, and Google scholar. The search was mainly focused on the role of naringin in various cardiovascular disorders in experimental animals. Based on the inclusion and exclusion criteria 34 studies were selected. The meta-analysis revealed that naringin could significantly alleviate various physical and chemical stimuli induced cardiovascular disorders such as diabetic cardiomyopathy, ischemic heart diseases, oxidative stress-induced cardiac injury, diet-induced cardiovascular dysfunctions in experimental models involving multiple mechanisms such as antioxidant (ROS/RNS pathways), anti-inflammatory (COX-2, IL-6, TNF-α, NF-κB pathways), enhancing angiogenic factors (VEGF, VCAM, HIF-1α, iNO), suppressing the apoptotic factors (BCL-2, BAX, caspases) and modulation of PCSK-9, PKCα/β, PPAR-α, JAK/STAT, MAPKs (p38α, ERK1/2, JNK), and PI3K/AKT/mTOR/p70S6K associated pathways. Further, these changes at the cellular and molecular levels were manifested as improvement in the structural, functional, and physiology of the heart upon the naringin treatment. In conclusion, this systematic review and meta-analysis support the available scientific evidence on the therapeutic benefits of naringin in the management of various cardiovascular conditions.

Background: Natural product-based cancer preventive and therapeutic entities, such as flavonoids and their derivatives, are shown to have a noticeable capability to suppress tumor formation and cancer cell growth. Naringin, a natural flavanone glycoside present in various plant species, has been indicated to modulate different signaling pathways and interact with numerous cell signaling molecules, which allows for an extensive variety of pharmacological actions, such as amelioration of inflammation, oxidative stress, metabolic syndromes, bone disorders, and cancer. The purpose of this systematic review is to present a critical and comprehensive assessment of the antitumor ability of naringin and associated molecular targets in various cancers. Methods: Studies were identified through systematic searches of Science Direct, PubMed, and Scopus as well as eligibility checks according to predefined selection criteria. Results: Eighty-seven studies were included in this systematic review. There was strong evidence for the association between treatment with naringin alone, or combined with other drugs and antitumor activity. Additionally, studies showed that naringin-metal complexes have greater anticancer effects compared to free naringin. It has been demonstrated that naringin employs multitargeted mechanisms to hamper cancer initiation, promotion, and progression through modulation of several dysregulated signaling cascades implicated in cell proliferation, autophagy, apoptosis, inflammation, angiogenesis, metastasis, and invasion. Conclusion: The results of our work show that naringin is a promising candidate for cancer prevention and treatment, and might offer substantial support for the clinical application of this phytocompound in the future. Nevertheless, further preclinical and clinical studies as well as drug delivery approaches are needed for designing novel formulations of naringin to realize the full potential of this flavonoid in cancer prevention and intervention.