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Structures of ginkgolides and bilobalide in Gingko biloba . ( A ) Ginkgolide A; ( B ) ginkgolide B; ( C ) ginkgolide J; and ( D ) bilobalide.
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Alzheimer's disease (AD) is one of the most well-known neurodegenerative diseases and explains 50-60% of dementia in patients. The prevalence rate of AD is positively correlated with age and AD affects ≥ 40% of those over 85 years old. The major AD therapeutics available on the market are acetylcholinesterase inhibitors, such as tacrine and donepez...
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... extract of G. biloba leaves which contains 24% flavonoid glycosides, 6% terpenoids, and 5-10% organic acids [46] has been extensively evaluated for its neuroprotective effects [47], and terpene trilactones ginkgolides are the major pharmacologically active constituents in EGb761. For example, pre-treatment of neuronal cells with ginkgolide A and B (Figure 2A,B) protects neuronal cells from synaptic damage evaluated by the loss of synaptophysin, a presynaptic synaptic marker [48] and increases neuronal survival against Aβ-induced toxicity [49]. Ginkgolide B rescues hippocampal neurons from Aβ-induced apoptosis by increasing the production of brain-derived neurotrophic factor [50] and reduces apoptotic death of neuronal cells in hemorrhagic rat brain [51]. ...
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... B reverses the Aβ-induced reduction of ACh release from hippocampal brain slices, suggesting potential improvements in learning and memory deteriorated by Aβ [53]. Furthermore, Vitolo et al. reports that ginkgolide J ( Figure 2C) is the most potent inhibitor of Aβ-induced hippocampal neuronal cell death among the ginkgolides in EGb761 [54]. Additionally, bilobalide ( Figure 2D) reduces Aβ-induced synaptic loss and subsequently enhances hippocampal neurogenesis and synaptogenesis [55]. ...
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... Vitolo et al. reports that ginkgolide J ( Figure 2C) is the most potent inhibitor of Aβ-induced hippocampal neuronal cell death among the ginkgolides in EGb761 [54]. Additionally, bilobalide ( Figure 2D) reduces Aβ-induced synaptic loss and subsequently enhances hippocampal neurogenesis and synaptogenesis [55]. Bilobalide also rescues chick embryonic neurons from apoptosis induced by serum deprivation or staurosporine treatment [56,57]. ...
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The medicinal benefits of Plantago major have been acknowledged around the world for hundreds of years. This plant contains a number of effective chemical constituents including flavonoids, alkaloids, terpenoids, phenolic acid derivatives, iridoid glycosides, fatty acids, polysaccharides and vitamins which contribute to its exerting specific therap...
Citations
... These compounds and their derivatives, composed of isoprene (C5) units, can be classified into monoterpenes (C10), sesquiterpenes (C15), diterpenes (C20), triterpenes (C30), and polyterpenes based on the number of carbon atoms [17]. Studies have shown that terpenoids in plants have various functions, such as defense, disease resistance, allelopathy, and insect induction [18][19][20][21][22]. Research has also been conducted on terpenoid compounds in fungi [23][24][25][26][27], such as tetracyclines and pleuromutilin (Drosophilin B) [28,29]. ...
Caoyuanheimo-1 (Agaricus sp.) is a delectable mushroom native to Inner Mongolia, China, belonging to the Agaricus genus and valued for both its edible and medicinal properties. Although it has been cultivated to a certain extent, the molecular mechanisms regulating its development remain poorly understood. Building on our understanding of its growth and development conditions at various stages, we conducted transcriptomic and metabolomic studies to identify the differentially expressed genes (DEGs) and metabolites throughout its growth cycle. Simultaneously, we analyzed the synthesis pathways and identified several key genes involved in the production of terpenoids, which are secondary metabolites with medicinal value widely found in mushrooms. A total of 6843 unigenes were annotated, and 449 metabolites were detected in our study. Many of these metabolites and differentially expressed genes (DEGs) are involved in the synthesis and metabolism of amino acids, such as arginine, cysteine, methionine, and other amino acids, which indicates that the genes related to amino acid metabolism may play an important role in the fruiting body development of Caoyuanheimo-1. Succinic acid also showed a significant positive correlation with the transcriptional level changes of nine genes, including laccase-1 (TRINITY_DN5510_c0_g1), fruiting body protein SC3 (TRINITY_DN3577_c0_g1), and zinc-binding dihydrogenase (TRINITY_DN2099_c0_g1), etc. Additionally, seventeen terpenoids and terpenoid-related substances were identified, comprising five terpenoid glycosides, three monoterpenoids, two diterpenoids, one sesquiterpenoid, one sesterterpenoid, two terpenoid lactones, and three triterpenoids. The expression levels of the genes related to terpenoid synthesis varied across the three developmental stages.
... 127 Additionally, natural chemicals differ in both their action and structure; it is not pretentious to discover anti-AD remedies from natural herbal products. 128 Additionally, the FDA now only approves a few medicines for the treatment and diagnosis of AD. 129 Here, we are more focused on mainly current studies on the prospective benefits of employing a variety of traditional medicinal plants and their phytoconstituents to treat AD. ...
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline, memory loss, and impaired daily functioning. While there is currently no cure for AD, several pharmacotherapeutic targets and management strategies have been explored. Additionally, traditional medicinal plants have gained attention for their potential role in AD management. Pharmacotherapeutic targets in AD include amyloid-beta (Aβ) aggregation, tau protein hyperphosphorylation, neuroinflammation, oxidative stress, and cholinergic dysfunction. Traditional medicinal plants, such as Ginkgo biloba, Huperzia serrata, Curcuma longa (turmeric), and Panax ginseng, have demonstrated the ability to modulate these targets through their bioactive compounds. Ginkgo biloba, for instance, contains flavonoids and terpenoids that exhibit neuroprotective effects by reducing Aβ deposition and enhancing cerebral blood flow. Huperzia serrata, a natural source of huperzine A, has acetylcholinesterase-inhibiting properties, thus improving cholinergic function. Curcuma longa, enriched with curcumin, exhibits anti-inflammatory and antioxidant effects, potentially mitigating neuroinflammation and oxidative stress. Panax ginseng’s ginsenosides have shown neuroprotective and anti-amyloidogenic properties. The investigation of traditional medicinal plants as a complementary approach to AD management offers several advantages, including a lower risk of adverse effects and potential multi-target interactions. Furthermore, the cultural knowledge and utilization of these plants provide a rich source of information for the development of new therapies. However, further research is necessary to elucidate the precise mechanisms of action, standardize preparations, and assess the safety and efficacy of these natural remedies. Integrating traditional medicinal-plant-based therapies with modern pharmacotherapies may hold the key to a more comprehensive and effective approach to AD treatment. This review aims to explore the pharmacotherapeutic targets in AD and assess the potential of traditional medicinal plants in its management.
... Several natural saponins may act as exogenous antioxidants to combat AD by managing oxidative stress [192,193]. Ginsenoside Rh2, a rare ginsenoside with few reports on its neuroprotective effects compared to other similar molecules [194], has shown significant neuroprotective effects in a scopolamine-induced model of memory impairment in ICR mice. Ginsenoside Rh2 effectively managed MDA levels while increasing glutathione (GSH) levels and SOD activity in the brain, effectively inhibiting oxidative stress [195]. ...
Drug development for Alzheimer’s disease, the leading cause of dementia, has been a long-standing challenge. Saponins, which are steroid or triterpenoid glycosides with various pharmacological activities, have displayed therapeutic potential in treating Alzheimer’s disease. In a comprehensive review of the literature from May 2007 to May 2023, we identified 63 references involving 40 different types of saponins that have been studied for their effects on Alzheimer’s disease. These studies suggest that saponins have the potential to ameliorate Alzheimer’s disease by reducing amyloid beta peptide deposition, inhibiting tau phosphorylation, modulating oxidative stress, reducing inflammation, and antiapoptosis. Most intriguingly, ginsenoside Rg1 and pseudoginsenoside-F11 possess these important pharmacological properties and show the best promise for the treatment of Alzheimer’s disease. This review provides a summary and classification of common saponins that have been studied for their therapeutic potential in Alzheimer’s disease, showcasing their underlying mechanisms. This highlights the promising potential of saponins for the treatment of Alzheimer’s disease.
... is a bicyclic monoterpenoid of natural origin (Fig. 1). Monoterpenes are essential oil components with established beneficial effects on memory, carried out by different mechanisms of action -affecting acetylcholinesterase activity, reducing Aβ-aggregation and oxidative stress, etc. [1]. ...
Myrtenal (M) is a natural bicyclic monoterpenoid with poorly studied neuroprotective potential. Our previous results established memory improvement in rats accompanied by significantly increased brain acetylcholine (ACh) levels. Adamantane is used as a pharmacophore for new drugs design based on known pharmacological agents for the development of medicines with stronger effects or with different therapeutic properties. The aim of this study was to evaluate on male Wistar rats the memory-improving potential of two Myrtenal-Adamantane derivatives MDs (MD-197, MD-198), synthesized in Novosibirsk Institute of Organic Chemistry. Both substances (1 mg kg-1 b.wt.) and the referent Myrtenal (40 mg kg-1 b.wt.), were applied as intraperitoneal (i.p.) emulsions for 11 consecutive days. Memory status was evaluated via a Passive avoidance test (at the beginning and at the end of the experiment). Acetylcholine esterase (AChE) activity, noradrenaline (NA), and serotonin (5-HT) content in brain structures related to memory (cortex and hippocampus) were biochemically measured. Results demonstrated significant memory improvement after multiple applications of both MDs. The significant inhibition of hippocampal AChE activity after MD-197 and MD-198 treatment was accompanied by specific changes in monoamine levels in the cerebral cortex and hippocampus. MD-197 significantly increased brain NA and 5-HT content showing potential antidepressant properties. All established effects of the two Myrtenal-Adamantane conjugates were stronger than those of the natural Myrtenal. This research revealed for the first time MDs' improving memory capacity related to their AChE inhibiting activity and neuromodulatory ability. These original data provide a reason for further investigation of these new perspective substances on the experimental model of dementia.
... Several studies demonstrated potential neuroprotective effects of terpenes and its derivatives, and these effects can be appointed as a decrease in apoptotic cell death, neutralization of reactive oxygen species, and stabilization of the mitochondrial membrane potential (Parmar et al. 2013), and improvement of mitochondrial function in mouse Huntington's disease (HD) model . Terpenoids such as ginsenosides, ginkgolides, and cannabinoids, in addition to oleanolic acid, tenuifolin, cryptotanshinone, and ursolic acid have also been used in therapy to AD acting directly or indirectly in the CNS (Yoo and Park 2012). Oleanolic acid derivatives (Fig. 6), 2-cyano-3,12-dioxooleana-1,9-dien-28-oic acid (CDDO), ethylamide (CDDO-EA), and CDDO trifluoroethylamide (CDDO-TFEA), induce antioxidant response element (ARE) gene expression-mediated Nrf2, increasing endogenous antioxidant defense through quinone oxidoreductase 1 (NQO-1), heme oxygenase-1 (HO-1), and glutathione S-transferase-a3 in NSC-34 cells stably transfected with mutant G93A SOD1, and besides that, upregulating the expression of antioxidant enzymes and downregulating iNOS, COX-2, FasL, and TNF-α in the spinal cord of ALS mouse models, and upregulating mitochondrial biogenesis-related proteins such as peroxisome proliferator-activated receptor-γ co-activator 1α (PGC-1α) (Neymotin et al. 2011). ...
Amyotrophic lateral sclerosis (ALS) is a fatal illness characterized by progressive motor neuron degeneration. Conventional therapies for ALS are based on treatment of symptoms, and the disease remains incurable. Molecular mechanisms are unclear, but studies have been pointing to involvement of glia, neuroinflammation, oxidative stress, and glutamate excitotoxicity as a key factor. Nowadays, we have few treatments for this disease that only delays death, but also does not stop the neurodegenerative process. These treatments are based on glutamate blockage (riluzole), tyrosine kinase inhibition (masitinib), and antioxidant activity (edaravone). In the past few years, plant-derived compounds have been studied for neurodegenerative disorder therapies based on neuroprotection and glial cell response. In this review, we describe mechanisms of action of natural compounds associated with neuroprotective effects, and the possibilities for new therapeutic strategies in ALS.
... On the other hand, the mitogen-activated protein kinase (MAPKs) pathway including p38 mitogen-activated protein kinases (p38), c-Jun N-terminal kinase (JNK), and extracellular-regulated kinase (ERK) mediates apoptosis via the regulation of Bcl-2 proteins [10]. Numerous natural antioxidant compounds isolated from herbal medicines such as phenolic acids, flavonoids, alkaloids, and terpenoids have been demonstrated to exert anti-AD properties in Aβ-induced neuronal cell death [11][12][13]. ...
Amyloid-beta (Aβ) aggregation and deposition have been identified as a critical feature in the pathology of Alzheimer’s disease (AD), with a series of functional alterations including neuronal oxidative stress and apoptosis. N-feruloyl serotonin (FS) is a plant-derived component that exerts antioxidant activity. This study investigated the protective effects of FS on Aβ25–35-treated neuronal damage by regulation of oxidative stress and apoptosis in human neuroblastoma SH-SY5Y cells. The radical scavenging activities increased with the concentration of FS, exhibiting in vitro antioxidant activity. The Aβ25–35-treated SH-SY5Y cells exerted neuronal cell injury by decreased cell viability and elevated reactive oxygen species, but that was recovered by FS treatment. In addition, treatment of FS increased anti-apoptotic factor B-cell lymphoma protein 2 (Bcl-2) and decreased the pro-apoptotic factor Bcl-2-associated X protein. The FS attenuated Aβ-stimulated neuronal apoptosis by regulations of mitogen-activated protein kinase signaling pathways. Moreover, activated CREB-BDNF signaling was observed by the treatment of FS in Aβ25–35-induced SH-SY5Y cells. These results demonstrate that FS shows potential neuroprotective effects on Aβ25–35-induced neuronal damage by attenuation of oxidative stress and apoptosis, and suggest that FS may be considered a promising candidate for the treatment of AD.
... Moreover, researchers had found that UA, as a ubiquitous pentacyclic triterpene with an effectively antioxidative activity, could reverse the neurotoxic effect in rat brains by improving the activities of anti-oxidant enzymes, SOD, CAT, GPx, and GR and reducing activated oxygen species content, and in this way boost the memory function in the hippocampal tissues (39). Experimental studies have also shown that UA supplementation could improve the toxic effects of free radicals in middle-aged rats' hippocampus and boost memory (40,41). Our study measured the activities of antioxidative enzymes, including CAT, SOD, GPx, and GSH, in the rat brain hippocampus. ...
Objective(s)
The increase in age-related cognitive impairment (CIs) and diabetes mellitus is a global health concern. Exercise training has been reported to activate the Nrf2/Keap1/ARE signaling and enhance the antioxidant defense pathways in some animal models. This study aimed to investigate the effects of ursolic acid (UA) associated with resistance or endurance training on antioxidant markers, and the Nrf2/Keap1/ARE pathway in the brain of older diabetic rats.
Materials and Methods
23-month-aged diabetes induced male Wistar rats were randomly assigned to seven groups (n=8). UA supplementation (250 mg/kg, daily) was administered along with resistance (60% maximum capacity of voluntary carrying [MVCC], 14-20 climbs) or endurance training (60-75% velocity at maximal oxygen uptake [vVO2max]), five days/week for eight weeks. Cognitive-motor functioning was assessed through open-field and passive avoidance response tests. Nrf2, Keap1, and antioxidant markers including SOD, CAT, GPx, and GSH were measured in the hippocampus tissue.
Results
The results showed positive effect of resistance training (P≤0.001) on Nrf2. There was endurance training with supplementation main effect (P=0.018) on Keap1 concentration. SOD revealed a significant endurance/resistance training by supplementation interaction effect (P≤0.05); however, there was no main training or UA supplementation effects on CAT, GPx, and GSH, despite improving spatial memory changes in exercise or UA groups.
Conclusion
It appears that UA treatment with resistance or endurance exercise has some beneficial effects on Nrf2 and some antioxidant markers. However, more research is needed to elucidate UA’s interaction effects and exercise interventions in diabetic situations.
... sativa). Terpenes are naturally occurring aliphatic compounds that are the main constituents of essential oils that have been associated with a multitude of bioactive properties (Nuutinen, 2018), providing protection against a range of stressors associated with neurodegenerative conditions such as inflammation and oxidative stress and more specifically, mitigation of amyloid β (Aβ) protein-evoked neurotoxicity as a pathological hallmark of Alzheimer's disease (AD) (Shin et al., 2020;Yoo & Park, 2012). ...
... For example, the appearance of senile plaques or brain lesions with deposits of b-amyloid (Ab) protein among neurons is one of the first features of Alzheimer diseases' patients [15,16]. Also, the deficiency of acetylcholine is also linked to neuronal loss and hence the propagation of Alzheimer's disease [17]. ...
... The actions on LXR-mediated transcription of the isolated sterol compounds from Sargassum fusiforme using reporter assay were also reported [111]. The isolated sterols were saringosterol, fucosterol, 29-hydroperoxy-stigmasta-5,24(28)-dien-3b-ol (14), 24-hydroperoxy-24-vinylcholesterol (15), 24-keto-cholesterol (16), 24-methylene-cholesterol and 5a,8a-epidioxyergosta-5. Sterols as potential therapeutic agents in neurodegenerative illnesses 6,22-dien-3b-ol (17). The study concluded that the potent activity of saringosterol was evidenced among the tested compounds by stimulating transcriptional activities of LXR either a or b with by 3.81 AE 0.15-fold and 14.40 AE 1.10-fold, respectively. ...
... In addition, the identification of M and C in several Salvia species, such as M in S. lachnostachys leaves [38] , S. multicaulis aerial parts [39] , and flowers of S. miltiorrhiza [40] , as well as C in leaf extract of S. officinalis [41] , aerial parts of S. mellifera [42] and S. plebeia [43] , flowers of S. miltiorrhiza [40] , and S. chinensis [44] have been published. Terpenoids, including U and O , are potential AChE inhibitors and thus possible agents in the ther-apy of Alzheimer's disease [45] . However, in our HPTLC-AChE assay, none of the four identified triterpenes showed activity. ...
Ethyl acetate extracts of Tunisian Salvia aegyptiaca and S. verbenaca aerial parts, and S. officinalis leaves, were examined via bioanalytical profiling using high-performance thin-layer chromatography (HPTLC) combined with antibacterial (Aliivibrio fischeri, Bacillus subtilis, and Rhodococcus fascians), antifungal (Bipolaris sorokiniana, and Fusarium avenaceum), radical scavenging (DPPH·), and enzyme inhibitory (α-glucosidase, acetylcholinesterase, and lipase) assays. The screening, using toluene - ethyl acetate – methanol 6:3:0.5 (V/V/V) as a mobile phase, revealed five bioactive zones (a-e) that were analyzed by HPTLC-electrospray ionization-mass spectrometry (ESI-MS). Zones b and c, observed exclusively in S. officinalis, were active in all assays except α-glucosidase, and only c inhibited F. avenaceum. Compounds in these zones were identified by HPLC-high resolution tandem MS (LC-HRMS/MS) as rosmanol/epi-rosmanol and methyl carnosate, respectively. In the bioactive zones a and e, corosolic/maslinic acids and ursolic/oleanolic acids isomer pairs were present, which could be identified in all three Salvia species after their HPTLC separation using pre-chromatographic derivatization with iodine and MS detection. The triterpenes inhibited B. subtilis and R. fascians bacteria and α-glucosidase enzyme. Linoleic and linolenic acids were detected in zone d, which showed strong lipase inhibition in all three sage species.
