Antioxidant Features of Humic Products by ABTS Assay.

Oxidative stress plays a pivotal role in driving immunosenescence by disrupting cellular homeostasis and impairing immune function. Humic substances exhibit scavenging activity against reactive oxygen species (ROS), inhibit ROS generation via metal chelation, and modulate endogenous antioxidant enzyme activity. Additionally, humic substances display anti-inflammatory effects, further supporting cellular redox balance. Given their antioxidant activity, humic substances hold promise as natural compounds for mitigating oxidative stress-associated immunosenescence. Here we describe the evaluation of antioxidant capacities of humic products by ABTS spectrophotometric assay.

Discovery of benzo[c]phenanthridine derivatives with potent activity against multidrug-resistant Mycobacterium tuberculosis.

Mycobacterium tuberculosis (Mtb), the pathogen responsible for tuberculosis (TB), is the leading cause of bacterial disease-related death worldwide. Current antibiotic regimens for the treatment of TB remain dated and suffer from long treatment times as well as the development of drug resistance. As such, the search for novel chemical modalities that have selective or potent anti-Mtb properties remains an urgent priority, particularly against multidrug-resistant (MDR) Mtb strains. Herein, we design and synthesize 35 novel benzo[c]phenanthridine derivatives (BPDs). The two most potent compounds, BPD-6 and BPD-9, accumulated within the bacterial cell and exhibited strong inhibitory activity (MIC90 ~2 to 10 µM) against multiple Mycobacterium strains while remaining inactive against a range of other Gram-negative and Gram-positive bacteria. BPD-6 and BPD-9 were also effective in reducing Mtb survival within infected macrophages, and BPD-9 reduced the burden of Mycobacterium bovis BCG in the lungs of infected mice. The two BPD compounds displayed comparable efficacy to rifampicin (RIF) against non-replicating Mtb (NR-Mtb). Importantly, BPD-6 and BPD-9 inhibited the growth of multiple MDR Mtb clinical isolates. Generation of BPD-9-resistant mutants identified the involvement of the Mmr efflux pump as an indirect resistance mechanism. The unique specificity of BPDs to Mycobacterium spp. and their efficacy against MDR Mtb isolates suggest a potential novel mechanism of action. The discovery of BPDs provides novel chemical scaffolds for anti-TB drug discovery.IMPORTANCEThe emergence of drug-resistant tuberculosis (TB) is a serious global health threat. There remains an urgent need to discover new antibiotics with unique mechanisms of action that are effective against drug-resistant Mycobacterium tuberculosis (Mtb). This study shows that novel semi-synthetic compounds can be derived from natural compounds to produce potent activity against Mtb. Importantly, the identified compounds have narrow spectrum activity against Mycobacterium species, including clinical multidrug-resistant (MDR) strains, are effective in infected macrophages and against non-replicating Mtb (NR-Mtb), and show anti-mycobacterial activity in mice. These new compounds provide promising chemical scaffolds to develop potent anti-Mtb drugs of the future.

Comprehensive Computational Screening and Analysis of Natural Compounds Reveals Promising Estrogen Receptor Alpha Inhibitors for Breast Cancer Therapy.

Breast cancer remains a leading cause of death among women, with estrogen receptor alpha (ERα) overexpression playing a pivotal role in tumor growth and progression. This study aimed to identify novel ERα inhibitors from a library of 561 natural compounds using computational techniques, including virtual screening, molecular docking, and molecular dynamics simulations. Four promising candidates-Protopine, Sanguinarine, Pseudocoptisine, and Stylopine-were selected based on their high binding affinities and interactions with key ERα residues. Molecular dynamics simulations conducted over 500 nanoseconds revealed that Protopine and Sanguinarine exhibited more excellent stability with minimal fluctuations, suggesting strong and stable binding. In contrast, Pseudocoptisine and Stylopine showed higher flexibility, indicating less stable interactions. Binding free energy calculations further supported the potential of Protopine and Sanguinarine as ERα inhibitors, though their binding strength was slightly lower than that of the reference compound. These findings highlight Protopine and Sanguinarine as leading candidates for further investigation, and in vitro and in vivo studies are recommended to evaluate their therapeutic potential in breast cancer treatment.

Natural and Nature-Inspired Catechol Siderophores: A Promising Strategy for Rice Blast Management.

The rice-blast fungus Pyricularia oryzae poses a significant threat to rice production worldwide. Ferroptosis, an iron-dependent form of regulated cell death, has recently been reported to be involved in P. oryzae pathogenicity during plant-fungal interactions. Ferroptosis regulates the developmental cell death of conidia necessary for appressorium maturation. In this study, we have established that a series of benzamides containing a chelating catechol moiety suppresses the formation/maturation of appressoria, which are essential for host infection by the rice blast fungus. Moreover, for the most active compounds we have shown that their activity can be at least partially reversed by adding exogenous Fe3+. These results highlight the close association between iron availability and appressorium maturation, opening new avenues for the development of targeted strategies for P. oryzae management.

A comprehensive review of natural compounds and their structure-activity relationship in Parkinson's disease: exploring potential mechanisms.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the progressive loss of dopamine-producing cells in the Substantia nigra region of the brain. Complementary and alternative medicine approaches have been utilized as adjuncts to conventional therapies for managing the symptoms and progression of PD. Natural compounds have gained attention for their potential neuroprotective effects and ability to target various pathways involved in the pathogenesis of PD. This comprehensive review aims to provide an in-depth analysis of the molecular targets and mechanisms of natural compounds in various experimental models of PD. This review will also explore the structure-activity relationship (SAR) of these compounds and assess the clinical studies investigating the impact of these natural compounds on individuals with PD. The insights shared in this review have the potential to pave the way for the development of innovative therapeutic strategies and interventions for PD.

Natural Autophagy Activators to Fight Age-Related Diseases.

The constant increase in the elderly population presents significant challenges in addressing new social, economic, and health problems concerning this population. With respect to health, aging is a primary risk factor for age-related diseases, which are driven by interconnected molecular hallmarks that influence the development of these diseases. One of the main mechanisms that has attracted more attention to aging is autophagy, a catabolic process that removes and recycles damaged or dysfunctional cell components to preserve cell viability. The autophagy process can be induced or deregulated in response to a wide range of internal or external stimuli, such as starvation, oxidative stress, hypoxia, damaged organelles, infectious pathogens, and aging. Natural compounds that promote the stimulation of autophagy regulatory pathways, such as mTOR, FoxO1/3, AMPK, and Sirt1, lead to increased levels of essential proteins such as Beclin-1 and LC3, as well as a decrease in p62. These changes indicate the activation of autophagic flux, which is known to be decreased in cardiovascular diseases, neurodegeneration, and cataracts. The regulated administration of natural compounds offers an adjuvant therapeutic alternative in age-related diseases; however, more experimental evidence is needed to support and confirm these health benefits. Hence, this review aims to highlight the potential benefits of natural compounds in regulating autophagy pathways as an alternative approach to combating age-related diseases.

Computational analysis of natural compounds as potential phosphodiesterase type 5A inhibitors.

Phosphodiesterase type 5 (PDE5) is a cyclic nucleotide-hydrolyzing enzyme that plays essential roles in the regulation of second messenger cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) produced in response to various stimuli. Pharmacological inhibition of PDE5 has been shown to have several therapeutic uses, including treating cardiovascular diseases and erectile dysfunction. In search of PDE5A inhibitors with safer pharmacokinetic properties, computational analyses of the binding propensity of fifty natural compounds comprising flavonoids, polyphenols, and glycosides were conducted. Molecular dynamics simulation coupled with Molecular mechanics with generalized Born and surface area solvation (MM/GBSA) showed that verbascoside may inhibit the activity of PDE5 with a comparative binding energy (ΔG) of -87.8 ± 9.2 kcal/mol to that of the cocrystal ligand (PDB ID: 3BJC), having ΔG = -77.7±4.5 kcal/mol. However, the other top compounds studied were found to have lower binding propensities than the cocrystal ligand WAN: hesperidin (ΔG = -33.8 ± 3.4 kcal/mol), rutin (ΔG = -23.6 ± 26.3 kcal/mol), caftaric acid (ΔG = -21.2 ±3.6 kcal/mol), and chlorogenic acid (ΔG = 6.0 ± 16.5 kcal/mol). Therefore, verbascoside may serve as a potential PDE5A inhibitor while hesperidin, rutin, and caftaric acid may provide templates for further structural optimization for the designs of safer PDE5 inhibitors.

Oxidative stress and culture atmosphere effects on bioactive compounds and laccase activity in the white rot fungus Phlebia radiata on birch wood substrate.

Wood-decaying white rot fungi live in changing environmental conditions and may switch from aerobic to fermentative metabolism under oxygen depletion. Decomposition of wood and lignocellulose by fungi is dependent on enzymatic and oxidative biochemistry including generation of reactive oxygen species. In this study, we subjected semi-solid wood-substrate cultures of the white rot fungus Phlebia radiata to oxidative stress by addition of hydrogen peroxide under aerobic and anaerobic cultivation conditions. Wood decomposition and fungal metabolism were followed by analysis of extracellular organic compounds, mycelial growth, and laccase activity. Under both atmospheric conditions, accumulation of bioactive aromatic compounds from birch wood occurred into the culture supernatants after hydrogen peroxide treatment. The supernatants inhibited both fungal growth and laccase activity. However, the fungus recovered from the oxidative stress quickly in a few days, especially when cultivated under regular aerobic conditions. With repeated hydrogen peroxide treatments, laccase suppressive-recovery effect was observed. Culture supernatants demonstrated antioxidant and antimicrobial effects, in concert with emergence of chlorinated birch-derived organic compounds. Bioactivities in the cultures disappeared in the same pace as the chlorinated compounds were transformed and de-chlorinated by the fungus. Our results indicate tolerance of white rot fungi against excessive oxidative stress and wood-derived, growth-inhibiting and harmful agents.

Curcumin is an efficacious therapeutic agent against Chilodonella uncinata via interaction with tubulin alpha chain as protein target.

Chilodonella, a parasitic ciliate that infects both cold water and warm water fish, can impede the growth of juvenile fish and cause considerable economic losses globally to freshwater aquaculture. In this study, the parasite was collected from both the gills and zygotes of largemouth bass (Micropterus salmoides). Isolated from diseased fish, the parasites were identified as Chilodonella uncinata based on morphological features and genetical diagnostic characterization using the partial small subunit ribosomal RNA gene. To develop an effective approach to treat chilodonellosis caused by C. uncinata in largemouth bass farming, we first developed an in vivo culture model for propagating C. uncinate and thus could use for morphological characterization, molecular analyses and antiparasitic drug screening. Curcumin was successfully identified as an efficacious anti-C. uncinata agent from 26 phytochemical compounds. When administered at a concentration of 6 mg/L, curcumin not only completely cured infected largemouth bass but also shielded uninfected fish from C. uncinata infections. The 24 h median effective concentration (EC50) of curcumin against C. uncinata was 3.098 mg/L. Remarkably, the 96 h median lethal concentration (LC50) of curcumin against largemouth bass was determined to be 17.143 mg/L, approximately 5.533 times higher than EC50. The mechanism of action of curcumin was investigated by the cellular thermal shift assay, demonstrating that tubulin alpha chain was the binding target for curcumin. Moreover, SEM investigations further provided morphological evidence suggesting that curcumin induces parasite demise by disrupting the parasite's body surface and subsequently infiltrating its interior. These findings collectively emphasize the potential of curcumin as a safe and effective therapeutic agent for controlling C. uncinata in aquaculture.

Herbal Remedies for Hepatic Inflammation: Unravelling Pathways and Mechanisms for Therapeutic Intervention.

Inflammation is a universal response of mammalian tissue to harm, comprising reactions to injuries, pathogens, and foreign particles. Liver inflammation is commonly associated with hepatocyte necrosis and apoptosis. These forms of liver cell injury initiate a sequence of events independent of the etiological basis for the inflammation and can result in hepatic disorders. It is also common for liver cancer. This review fundamentally focuses on the molecular pathways involved in hepatic inflammation. This review aims to explore the molecular pathways involved in hepatic inflammation, focusing on arachidonic acid, NF-κB, MAPK, PI3K/Akt, and JAK/STAT pathways. It investigates active compounds in herbal plants and their pharmacological characteristics. The review proposes a unique therapeutic blueprint for managing hepatic inflammation and diseases by modifying these pathways with herbal remedies.

Antibiotics-free compounds for managing carbapenem-resistant bacteria; a narrative review.

Carbapenem-resistant (CR) Gram-negative bacteria have become a significant public health problem in the last decade. In recent years, the prevalence of CR bacteria has increased. The resistance to carbapenems could result from different mechanisms such as loss of porin, penicillin-binding protein alteration, carbapenemase, efflux pump, and biofilm community. Additionally, genetic variations like insertion, deletion, mutation, and post-transcriptional modification of corresponding coding genes could decrease the susceptibility of bacteria to carbapenems. In this regard, scientists are looking for new approaches to inhibit CR bacteria. Using bacteriophages, natural products, nanoparticles, disulfiram, N-acetylcysteine, and antimicrobial peptides showed promising inhibitory effects against CR bacteria. Additionally, the mentioned compounds could destroy the biofilm community of CR bacteria. Using them in combination with conventional antibiotics increases the efficacy of antibiotics, decreases their dosage and toxicity, and resensitizes CR bacteria to antibiotics. Therefore, in the present review article, we have discussed different aspects of non-antibiotic approaches for managing and inhibiting the CR bacteria and various methods and procedures used as an alternative for carbapenems against these bacteria.

Assessment of antiemetic activity of dihydrocoumarin: In vivo and in silico approaches on receptor binding affinity and modulatory effects.

Dihydrocoumarin (DCN) is a natural compound widely used in the flavor industry and has antioxidant and anti-inflammatory properties. However, its potential antiemetic effects on gastrointestinal disturbances remain untested. This study emphasizes assessing the antiemetic properties of the natural aromatic compound DCN using copper sulfate (CuSO4.5H2O)-induced emetic model on chicks, and an in silico approach was also adopted to estimate the possible underlying mechanisms. Two doses (25 and 50 mg/kg b.w.) of DCN and several referral drugs considered positive controls (PCs), including domperidone (6 mg/kg), hyoscine (21 mg/kg), aprepitant (16 mg/kg), diphenhydramine (10 mg/kg), and ondansetron (5 mg/kg), were orally administered to chicks. The vehicle was provided as the control group. Co-treatments of DCN with referral drugs were also provided to chicks to evaluate the modulatory action of the test compound. According to the results, DCN delayed the emetic onset and decreased the frequency of retches in a dose-dependent manner compared to the vehicle group. DCN (50 mg/kg) represented a notable delayed latency period (61.17 ± 4.12 s) and a diminished number of retchings (17.67 ± 1.82 times) compared to the control group. Further, in the co-treatments, DCN increased the latency period and reduced the number of retches, except for domperidone. In the in silico investigation, DCN showed notable binding affinity toward the D2 (-7 kcal/mol), H1 (-7.5 kcal/mol), and M5 (-7 kcal/mol) receptors in the same binding site as the referral ligand. Our research indicates that DCN has mild antiemetic properties by interacting with the D2, H1, and M5 receptors. Therefore, several pre-clinical and clinical studies are necessary to assess the effectiveness and safety profile of this food ingredient.

Natural Compounds for Bone Remodeling: Targeting osteoblasts and relevant signaling pathways.

In the process of bone metabolism and bone remodeling, bone marrow mesenchymal stem cells (BM-MSCs) differentiate into osteoblasts (OBs) under certain conditions to enable the formation of new bone, and normal bone reconstruction and pathological bone alteration are closely related to the differentiation and proliferation functions of OBs. Osteogenic differentiation of BM-MSCs involves multiple signaling pathways, which function individually but interconnect intricately to form a complex signaling regulatory network. Natural compounds have fewer adverse effects than chemically synthesized drugs, optimize bone health, and are more suitable for long-term use. In this paper, we focus on OBs, summarize the current research progress of signaling pathways related to OBs differentiation, and review the molecular mechanisms by which chemically synthesized drugs with potential anti-osteoporosis properties regulate OBs-mediated bone formation.

Bioactive Insecticides from Chemometric Diverse Ant-Associated Symbionts Streptomyces novaecaesareae and Streptomyces nojiriensis against the Fall Armyworm Larvae.

The Streptomyces genus has long been recognized as a prolific and valuable source of diverse secondary metabolites. These metabolites contribute significantly to the intricate chemical diversity exhibited by Streptomyces, making them an indispensable reservoir for drug discovery, agricultural applications, and industrial processes. Exploiting the potential of these natural compounds holds the promise of ushering in a new era in insect pest management, reducing reliance on synthetic chemicals and fostering ecologically sustainable solutions. This study dives into the realm of chemo diversity within isolates of Streptomyces nojiriensis and Streptomyces novaecaesareae, with a specific focus on the production of insecticidal compounds. We explored chromatographic techniques for the identification and isolation of insecticidal compounds, and two bioactive compounds were identified in extracts of S. novaecaesareae. Valinomycin was identified from hexanic extracts of strain Asp59, while naphthomycin from ethyl acetate extracts of strain Asp58. These compounds showed insecticidal activity against first instars of Spodoptera frugiperda (Asp59: LC50 = 10.82 µg/µL, LC90 = 26.25 µg/µL; Asp58: LC50 = 15.05 µg/µL, LC90 = 38.84 µg/µL). Notably, this is the first report of naphthomycin as an insecticidal compound. The present study suggests that valinomycin and naphthomycin may be a novel biological source for the control of Spodoptera frugiperda in early stages.

Therapeutic Potential and Mechanisms of Bee Venom Therapy: A Comprehensive Review of Apitoxin Applications and Safety Enhancement Strategies.

Apitoxin therapy (BVT-bee venom therapy) is an emerging complementary treatment utilizing bee venom for various medical conditions. This review explores the potential and therapeutic mechanisms of bee venom, focusing on its chemical composition and the methods for its extraction and purification to enhance safety while maintaining bioactivity. Bee venom contains amphipathic peptides such as melittin and apamin, enzymes like phospholipase A2, and bioamines including histamine and catecholamines, contributing to its pleiotropic effects. The therapeutic applications of bee venom span anti-inflammatory, analgesic, antimicrobial, antiviral, neuroprotective, anti-arthritic, and anti-cancer activities. Clinical and laboratory studies have demonstrated its efficacy in treating chronic and autoimmune diseases, pain management, and improving quality of life. The immunogenic properties of bee venom necessitate ongoing research to mitigate allergic reactions, ensuring its safe and effective use in medical practice. This review summarizes the current state of research on bee venom therapy, highlighting its potential benefits and future research directions.

Acetylation of Oleanolic Acid Dimers as a Method of Synthesis of Powerful Cytotoxic Agents.

Oleanolic acid, a naturally occurring triterpenoid compound, has garnered significant attention in the scientific community due to its diverse pharmacological properties. Continuing our previous work on the synthesis of oleanolic acid dimers (OADs), a simple, economical, and safe acetylation reaction was performed. The newly obtained derivatives (AcOADs, 3a-3n) were purified using two methods. The structures of all acetylated dimers (3a-3n) were determined based on spectral methods (IR, NMR). For all AcOADs (3a-3n), the relationship between the structure and the expected directions of pharmacological activity was determined using a computational method (QSAR computational analysis). All dimers were also tested for their cytotoxic activity on the SKBR-3, SKOV-3, PC-3, and U-87 cancer cell lines. HDF cell line was applied to evaluate the Selectivity Index of the tested compounds. All cytotoxic tests were performed with the application of the MTT assay. Finally, all dimers of oleanolic acid were subjected to DPPH and CUPRAC tests to evaluate their antioxidant activity. The obtained results indicate a very high level of cytotoxic activity (IC50 for most AcOADs below 5.00 µM) and a fairly high level of antioxidant activity (Trolox equivalent in some cases above 0.04 mg/mL).

Oxyresveratrol Enhances the Anti-Cancer Effect of Cisplatin against Epithelial Ovarian Cancer Cells through Suppressing the Activation of Protein Kinase B (AKT).

Epithelial ovarian carcinoma poses a significant challenge due to its resistance to chemotherapy and propensity for metastasis, thereby reducing the effectiveness of conventional treatments. Hence, the identification of novel compounds capable of augmenting the anti-cancer efficacy of platinum-based chemotherapy is imperative. Oxyresveratrol (OXY), a derivative of resveratrol, has been demonstrated to possess antiproliferative and apoptosis-inducing effects across various cancer cell lines. Notably, OXY appears to exert its effects by inhibiting the PI3K/AKT/mTOR signaling pathway. However, the synergistic potential of OXY in combination with cisplatin against epithelial ovarian cancer has not yet been elucidated. The current study investigated the synergistic effects of OXY and cisplatin on the ovarian cancer cell lines SKOV3 and TOV21G. We found that OXY significantly enhanced cisplatin's ability to reduce cell viability, induce apoptosis, induce cell cycle arrest, and increase the proportion of cells in the sub-G1 phase. Furthermore, OXY treatment alone dose-dependently inhibited the production of anti-apoptotic proteins including Mcl-1, Bcl-xL, and XIAP under EGF activation. Mechanistically, OXY suppressed the PI3K/AKT/mTOR signaling pathway by reducing phosphorylated AKT, while having no discernible effect on the MAPK pathway. These findings highlight OXY's potential to enhance ovarian cancer cell sensitivity to chemotherapy, suggesting its development as a pharmaceutical adjunct for clinical use in combination therapies.

Utilizing Indigenous Flora in East Africa for Breast Cancer Treatment: An Overview.

BACKGROUND: Breast cancer is a significant global health challenge, contributing substantially to cancer- related deaths. Conventional treatment methods, including hormone therapy, chemotherapy, surgical interventions, and radiation, have long been utilized. However, these traditional treatments are often associated with serious side effects and drug resistance, limiting their efficacy. AIM: This review aims to explore the potential of medicinal plants used in breast cancer management in East Africa, focusing on their bioactive compounds and anticancer properties. METHODS: A comprehensive literature search was conducted to examine the effectiveness of medicinal plants in treating breast cancer across Kenya, Ethiopia, Uganda, Tanzania, and Rwanda. Relevant studies published between 2003 and 2023 were identified using keywords related to breast cancer and medicinal plants. The search was performed across multiple databases, including Google Scholar, PubMed, Scopus, Web of Science Core Collection, and Science Direct. RESULTS: Numerous natural compounds found in East African medicinal plants including Cymbopogon citratus (Lemongrass,) Tabebuia avellanedae, Prunus africana (African Cherry), Euclea divinorum, Berberis holstii, Withania somnifera (Ashwagandha, Curcuma longa (Turmeric), Garcinia mangostana (Mangosteen, Vitis vinifera (Grapevine), Eugenia jambolana (Java Plum), Moringa oleifera (Drumstick Tree), Camellia sinensis (Tea), Glycine max (Soybean), Catharanthus roseus, Madagascar Periwinkle), Rhus vulgaris (Wild Currant) exhibit significant anticancer properties. These compounds have demonstrated the ability to reduce breast cancer aggressiveness, inhibit cancer cell proliferation, and modulate cancer-related pathways. Current research focuses on these natural and dietary compounds to develop more effective strategies for treating breast cancer. CONCLUSION: The findings suggested that East African medicinal plants hold promise as complementary treatments for breast cancer, offering potential benefits such as affordability, cultural appropriateness, and sustainability. Further research into these plants and their bioactive compounds could revolutionize breast cancer treatment, improving survival rates and addressing the rising incidence of breast cancer-related fatalities. Other: The review underscores the importance of continued research, conservation, and the integration of ancient healing methods to fully harness the potential of East African flora in breast cancer management.

Exploring the Potential of Herbal Compounds as Autophagy Modulators in Alzheimer's Disease: A Comprehensive Review.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder that causes atrophy of brain cells, leading to their death, and has become a leading cause of death in aging populations worldwide. AD is characterized by ß-amyloid (Aß) deposition and tau phosphorylation in neural tissues, but the precise pathophysiology of the disease is still obscure. Autophagy is an evolutionarily targeted mechanism that is necessary for the elimination of neuronal and glial misfolded proteins as well as proteins. It also plays an essential role in synaptic plasticity. The aberrant autophagy primarily influences the process of aging and neurodegeneration. Autophagy significantly influences how Aß and tau function physiologically, therefore, atypical autophagy is expected to perform an important role in Aß deposition and tau phosphorylation characteristic in the development of AD. Bioactive phytoconstituents could majorly contribute as a natural yet effective alternative approach to slow down the progression of neurodegeneration and promote the active aging process in elderly patients. Over the recent years, it is well evidenced that different secondary metabolites including polyphenols, alkaloids, terpenes, and phenols exhibited neuroprotective effects, and attenuated brain damage, and cognitive impairment in vitro as well as in vivo. Additionally, the underlying mechanism of action shared by them is the regulation of competent autophagy via the removal of aggregated protein and mitochondrial dysfunction. The present article is structured as a reference for researchers keen to investigate and assess the new natural compound-mediated therapeutic approach for AD treatment through the modulation of autophagy.