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Neuropharmacology of Plant Extracts and Their Active Compounds

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A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Natural Products".

Deadline for manuscript submissions: closed (28 February 2025) | Viewed by 21134

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Dr. Angel Josabad Alonso-Castro

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Departamento de Farmacia, División de Ciencias Naturales y Exactas, Universidad de Guanajuato, Guanajuato, Mexico
Interests: pharmacology; medicinal plant; ethnobotany; pharmacy
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Dear Colleagues,

Approximately 13% of the world's population, around 970 million people, lives with mental disorders that affect emotional regulation, as well as physical and social functions. The number of cases of anxiety and depression due to the pandemic situation has increased dramatically. A small percentage of people with a mental disorder will look for medical advice. In rural areas, it is difficult to access pharmacological treatments. The use of medicinal plants among the general population for treating mental disorders has increased during the last three years. Many of these plant species and their active compounds remain to be studied. This Special Issue will be focused on medicinal plants used for mental disorders on the following topics: (i) ethnobotanical studies using quantitative tools, (ii) survey-based studies about self-medication/use of herbal products, (iii) preclinical and clinical studies about neuropharmacological action of plant extracts and/or their active compounds, (v) legislation and regulation of herbal products used for mental disorders, (vi) herb–drug combinations, and (vii) herb–drug-based treatments for preventing neurodegenerative diseases.

The journal Pharmaceuticals invites experts to contribute to this Special Issue with reviews and original research articles focusing on the pharmacology, toxicology, analytical chemistry, pharmacy, and ethnobotany of medicinal plants with neuropharmacological effects.

Dr. Angel Josabad Alonso-Castro
Guest Editor

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Keywords

medicinal plant
mental disorder
preclinical
clinical

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Published Papers (10 papers)

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15 pages, 2575 KiB

Open AccessArticle

Antidepressant- and Anxiolytic-like Effects in Mice of Alkaloids from Aerial Parts of Argemone platyceras Link & Otto

by Mayra Beatriz Gómez-Patiño, Rosa Estrada-Reyes, Héctor Hugo Hernández-Mendoza, Ángela Suarez-Rojas and Daniel Arrieta-Baez

Pharmaceuticals 2025, 18(1), 49; https://doi.org/10.3390/ph18010049 - 3 Jan 2025

Viewed by 806

Abstract

Background/Objectives: Argemone platyceras Link & Otto, an endemic plant of Mexico, is widely distributed in the central area of the country, mainly in the states of Tlaxcala, Puebla, and the State of Mexico. Ethnobotanical studies in different communities of these states have demonstrated that it is primarily used to treat diabetes and mental illnesses, such as “los nervios” (nerves) and “el ansia” (anxiety); these terms are used in traditional medicine, but it is accepted that they refer to anxiety disorders. This study aimed to validate the traditional use of aerial parts of A. platyceras Link & Otto in treating these illnesses. Methods: a standardized acidic method to obtain alkaloids was used to obtain an extract (AlkExt), which was tested in adult male Swiss Webster mice in the tail suspension (TST) and forced swimming (FST) tests. Results: AlkExt was analyzed using mass spectrometry techniques (DI-ESI and UHPLC-MS) to detect 2,3′,4,5′-Tetramethoxystilbene (m/z 301.14, 3%), scoulerine (m/z 328.16, 19.8%), tetrahydro-columbamine (m/z 342.17, 28.8%), 8-(hydroxymethyl)-2,10-dimethoxy-6,8,13,13a-tetrahydro-5H-isoquinolino[2,1-b]isoquinoline-1,11-diol (m/z 358.17, 22.8%), and glaucine (m/z 356.19, 11.1%); these were assayed in a single oral administration of AlkExt, which caused robust anxiolytic- and antidepressant-like effects without affecting the spontaneous ambulatory activity of the mice. Conclusions: The easy and standardized AlkExt analyzed in pharmaceuticals assays in this study strongly suggest its therapeutic potential to treat the comorbidity of anxiety and depression disorders and support further investigations in people with these diseases. Full article

(This article belongs to the Special Issue Neuropharmacology of Plant Extracts and Their Active Compounds)

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21 pages, 2955 KiB

Open AccessArticle

Multivalent Neuroprotective Activity of Elettaria cardamomum (Cardamom) and Foeniculum vulgare (Fennel) in H₂O₂-Induced Oxidative Stress in SH-SY5Y Cells and Acellular Assays

by Himadri Sharma, Hyewon Yang, Niti Sharma and Seong Soo A. An

Pharmaceuticals 2025, 18(1), 2; https://doi.org/10.3390/ph18010002 - 24 Dec 2024

Viewed by 757

Abstract

Background: Elettaria cardamomum (Cardamom) and Foeniculum vulgare (Fennel) are well-known spices and are also used as natural mouth fresheners. This study was performed to evaluate their neuroprotective ability based on certain acellular and cellular assays. Methods: Hexane and ethyl acetate extracts were prepared using cardamom and fennel seeds. GC/MS was performed for the identification of important bioactive compounds. Cell-based assays were performed using SH-SY5Y cells. Hydrogen peroxide was used for the induction of oxidative stress, and evaluation was done based on neuroprotection, reduced reactive oxygen species, and restoration of mitochondrial membrane potential (MMP). Additionally, anti-Aβ fibrillization/oligomerization activities were also analyzed along with anti-acetylcholinesterase activity. Results: α-Terpinyl acetate and anethol were identified as major phytocompounds in cardamom and fennel, respectively. Cardamom extracts and α-terpinyl acetate were more potent acetylcholinesterase (AChE) inhibitors than fennel extracts and anethol [IC₅₀ cardamom extracts, 130–150 μg/mL; α-terpinyl acetate, 61.87 μg/mL; anethol, 374.2 μg/mL; fennel extracts, >1 mg/mL] and showed mixed-type inhibition. Only the extracts displayed potent anti-Aβ fibrilization activity (>50%). Anethol showed potent anti-Aβ oligomerization activity (>50%), followed by α-terpinyl acetate and fennel-H (~36%). The neuroprotective potential of the spice extracts/phytochemicals was evaluated in SH-SY5Y cells by using H₂O₂-induced oxidative stress. Cardamom-EA displayed the best neuroprotection (0.01 to 30 μg/mL). No neuroprotection was observed by α-terpinyl acetate and anethol. Cardamom extracts and fennel-H restored the normal reactive oxygen species (ROS) levels at 30 µg/mL and 1 µg/mL, respectively. Conclusion: Overall, the extracts provided better neuroprotection than the pure compounds in cellular assays and displayed strong anti-Aβ fibrilization activity. Full article

(This article belongs to the Special Issue Neuropharmacology of Plant Extracts and Their Active Compounds)

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14 pages, 1484 KiB

Open AccessArticle

Centella asiatica Promotes Antioxidant Gene Expression and Mitochondrial Oxidative Respiration in Experimental Autoimmune Encephalomyelitis

by Payel Kundu, Kanon Yasuhara, Mikah S. Brandes, Jonathan A. Zweig, Cody J. Neff, Sarah Holden, Kat Kessler, Steven Matsumoto, Halina Offner, Carin S. Waslo, Arthur Vandenbark, Amala Soumyanath, Larry S. Sherman, Jacob Raber, Nora E. Gray and Rebecca I. Spain

Pharmaceuticals 2024, 17(12), 1681; https://doi.org/10.3390/ph17121681 - 13 Dec 2024

Viewed by 1305

Abstract

Background/Objectives: Centella asiatica (L.) Urban (family Apiaceae) (C. asiatica) is a traditional botanical medicine used in aging and dementia. Water extracts of C. asiatica (CAW) have been used to treat neuropsychiatric symptoms in related animal models and are associated with increases in antioxidant response element (ARE) genes and improvements in mitochondrial respiratory function and neuronal health. Because multiple sclerosis (MS) shares its neurogenerative pathology of oxidative stress and mitochondrial dysfunction with aging and dementia, neuropsychiatric symptoms in MS may also benefit from C. asiatica. To determine whether CAW similarly benefits neuropsychiatric symptoms, ARE gene expression, and mitochondrial respiration in inflammatory models of MS, and to determine the effects of CAW on clinical disability and inflammation, we tested CAW using experimental autoimmune encephalomyelitis (EAE). Methods: C57BL/6J mice induced with EAE were treated with CAW or a placebo for 2 weeks. The outcomes were clinical disability, signs of anxiety (open field test), ARE gene expression, mitochondrial respiration, and inflammation and demyelination. Results: At the dosing schedule and concentrations tested, CAW-treated mice with EAE demonstrated increased ARE gene expression and mitochondrial respiratory activity compared to those of placebo-treated mice with EAE. CAW was also associated with reduced inflammatory infiltrates in the spinal cord, but the differences between the populations of activated versus quiescent microglia were equivocal. CAW did not improve behavioral performance, EAE motor disability, or demyelination. Conclusions: In the inflammatory EAE model of MS, CAW demonstrates similar neuroprotective effects to those it exhibits in aging and dementia mouse models. These benefits, along with the anti-inflammatory effects of CAW, support further investigation of its neuropsychiatric effects in people with MS. Full article

(This article belongs to the Special Issue Neuropharmacology of Plant Extracts and Their Active Compounds)

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19 pages, 5583 KiB

Open AccessArticle

(-)-Syringaresinol Exerts an Antidepressant-like Activity in Mice by Noncompetitive Inhibition of the Serotonin Transporter

by Yingyao Wu, Jianxin Cai, Hanhe Liu, Chan Li, Qingfa Tang and Yuan-Wei Zhang

Pharmaceuticals 2024, 17(12), 1637; https://doi.org/10.3390/ph17121637 - 5 Dec 2024

Viewed by 974

Abstract

Background: Albizia julibrissin Durazz. is one of the most popular herbs used for depression treatment, but the molecular basis for its mechanism of action has not been fully addressed. Previously, we isolated and identified two lignan glycoside derivatives that were shown to noncompetitively inhibit serotonin transporter (SERT) activity but with a relatively low inhibitory potency compared with those of conventional antidepressants. Methods: We characterized the pharmacological profile of the parental compound of these previously isolated lignan glycosides, (-)-syringaresinol (SYR), in inhibiting SERT by using biochemical, pharmacological, and behavioral approaches. Results: SYR, as a potent inhibitor, decreases SERT V_max but with little change in K_m for its fluorescent substrate. SYR was shown to block the conformational conversion essential for substrate transport by stabilizing SERT in an outward-open and inward-closed conformation. In addition, our molecular docking and biochemical validation demonstrated that SYR binds to an allosteric site in SERT and noncompetitively inhibits SERT transport and binding activity. Furthermore, administration of SYR was indicated to exert an antidepressant-like activity and to effectively attenuate chronic unpredictable mild stress (CUMS)-induced abnormalities in behaviors and synaptic protein expression in depressive animal models. Conclusions: This study not only provides molecular insights into the mechanism of action of A. julibrissin in the treatment of depression, but also opens up the possibility of development of a novel class of allosteric site-targeted therapeutic agents with an underlying mechanism of action different from that of conventional antidepressants. Full article

(This article belongs to the Special Issue Neuropharmacology of Plant Extracts and Their Active Compounds)

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22 pages, 9389 KiB

Open AccessArticle

Comparative Analysis of Volatile Components in Chi-Nan and Ordinary Agarwood Aromatherapies: Implications for Sleep Improvement

by Zixiao Jiang, Junyu Mou, Jian Feng, Shunan Zhang, Dan Li and Yangyang Liu

Pharmaceuticals 2024, 17(9), 1196; https://doi.org/10.3390/ph17091196 - 11 Sep 2024

Viewed by 1822

Abstract

Agarwood, a precious traditional medicinal herb and fragrant material, is known for its sedative and sleep-improving properties. This study explores the mechanisms underlying the aromatherapy effects of Chi-Nan agarwood and ordinary agarwood in improving sleep. Using a combination of gas chromatography–mass spectrometry (GC-MS), network pharmacology, and molecular docking techniques, we identified and c ompared the chemical compositions and potential molecular targets of both types of agarwood. The GC-MS analysis detected 87 volatile components across six types of agarwood aromatherapy, with 51 shared between Chi-Nan and ordinary agarwood, while each type also had 18 unique components. Ordinary agarwood was found to be richer in sesquiterpenes and small aromatic molecules, whereas Chi-Nan agarwood contained higher levels of chromones. These differences in chemical composition are likely responsible for the distinct sleep-improving effects observed between the two types of agarwood. Through network pharmacology, 100, 65, and 47 non-repetitive target genes related to sleep improvement were identified for components shared by both types of agarwood (CSBTs), components unique to common agarwood (CUCMs), and components unique to Chi-Nan agarwood (CUCNs), respectively. The constructed protein–protein interaction (PPI) networks revealed that key targets such as MAOA, MAOB, SLC6A4, and ESR1 are involved in the sleep-improving mechanisms of agarwood aromatherapy. Molecular docking further confirmed the strong binding affinities of major active components, such as 5-Isopropylidene-6-methyldeca-369-trien-2-one and 2-(2-Phenylethyl)chromone, with these core targets. The results suggest that agarwood aromatherapy enhances sleep quality through both hormonal and neurotransmitter pathways, with ordinary agarwood more deeply mediating hormonal regulation, while Chi-Nan agarwood predominantly influences neurotransmitter pathways, particularly those involving serotonin and GABA. This study provides valuable insights into the distinct therapeutic potentials of Chi-Nan and ordinary agarwood, highlighting their roles in sleep improvement and offering a foundation for future research in the clinical application of agarwood-based aromatherapy. Full article

(This article belongs to the Special Issue Neuropharmacology of Plant Extracts and Their Active Compounds)

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16 pages, 2448 KiB

Open AccessArticle

Methyleugenol Has an Antidepressant Effect in a Neuroendocrine Model: In Silico and In Vivo Evidence

by Mayara Cecile Nascimento Oliveira, Ikla Lima Cavalcante, Alana Natalícia de Araújo, Aline Matilde Ferreira dos Santos, Renata Priscila Barros de Menezes, Chonny Herrera-Acevedo, Natália Ferreira de Sousa, Jailane de Souza Aquino, José Maria Barbosa-Filho, Ricardo Dias de Castro, Reinaldo Nóbrega Almeida, Luciana Scotti, Marcus Tullius Scotti and Mirian Graciela Da Silva Stiebbe Salvadori

Pharmaceuticals 2023, 16(10), 1408; https://doi.org/10.3390/ph16101408 - 4 Oct 2023

Cited by 2 | Viewed by 1751

Abstract

Major depressive disorder is a severe mood disorder characterized by different emotions and feelings. This study investigated the antidepressant activity of the phenylpropanoid methyleugenol (ME) in adult female mice exposed to a stress model induced by dexamethasone. The animals were randomly divided into groups containing eight animals and were pre-administered with dexamethasone (64 μg/kg subcutaneously). After 165 and 180 min, they were treated with ME (25, 50 and 100 mg/kg intraperitoneally) or imipramine (10 mg/kg intraperitoneally) after 45 min and 30 min, respectively; they were then submitted to tests which were filmed. The videos were analyzed blindly. In the tail suspension test, ME (50 mg/kg) increased latency and reduced immobility time. In the splash test, ME (50 mg/kg) decreased grooming latency and increased grooming time. In the open field, there was no statistical difference for the ME groups regarding the number of crosses, and ME (50 mg/kg) increased the number of rearing and time spent in the center. Regarding in silico studies, ME interacted with dopaminergic D1 and α1 adrenergic pathway receptors and with tryptophan hydroxylase inhibitor. In the in vivo evaluation of the pathways of action, the antidepressant potential of ME (50 mg/kg) was reversed by SCH23390 (4 mg/kg intraperitoneally) dopaminergic D1 receptor, Prazosin (1 mg/kg intraperitoneally) α1 adrenergic receptor, and PCPA (4 mg/kg intraperitoneally) tryptophan hydroxylase inhibitor. Our findings indicate that ME did not alter with the locomotor activity of the animals and shows antidepressant activity in female mice with the participation of the D1, α1 and serotonergic systems. Full article

(This article belongs to the Special Issue Neuropharmacology of Plant Extracts and Their Active Compounds)

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20 pages, 3697 KiB

Open AccessArticle

Neuropharmacological Effects of the Dichloromethane Extract from the Stems of Argemone ochroleuca Sweet (Papaveraceae) and Its Active Compound Dihydrosanguinarine

by Eunice Yáñez-Barrientos, Juan Carlos Barragan-Galvez, Sergio Hidalgo-Figueroa, Alfonso Reyes-Luna, Maria L. Gonzalez-Rivera, David Cruz Cruz, Mario Alberto Isiordia-Espinoza, Martha Alicia Deveze-Álvarez, Clarisa Villegas Gómez and Angel Josabad Alonso-Castro

Pharmaceuticals 2023, 16(8), 1175; https://doi.org/10.3390/ph16081175 - 18 Aug 2023

Cited by 4 | Viewed by 2168

Abstract

Argemone ochroleuca Sweet (Papaveraceae) is used in folk medicine as a sedative and hypnotic agent. This study aimed to evaluate the anxiolytic-like, sedative, antidepressant-like, and anticonvulsant activities of a dichloromethane extract of A. ochroleuca stems (AOE), chemically standardized using gas chromatography–mass spectrometry (GC–MS), and its active compound dihydrosanguinarine (DHS). The anxiolytic-like, sedative, antidepressant-like, and anticonvulsant activities of the AOE (0.1–50 mg/kg p.o.) and DHS (0.1–10 mg/kg p.o.) were evaluated using murine models. A possible mechanism for the neurological actions induced by the AOE or DHS was assessed using inhibitors of neurotransmission pathways and molecular docking. Effective dose 50 (ED₅₀) values were calculated by a linear regression analysis. The AOE showed anxiolytic-like activity in the cylinder exploratory test (ED₅₀ = 33 mg/kg), and antidepressant-like effects in the forced swimming test (ED₅₀ = 3 mg/kg) and the tail suspension test (ED₅₀ = 23 mg/kg), whereas DHS showed anxiolytic-like activity (ED₅₀ = 2 mg/kg) in the hole board test. The AOE (1–50 mg/kg) showed no locomotive affectations or sedation in mice. A docking study revealed the affinity of DHS for α2-adrenoreceptors and GABA_A receptors. The anxiolytic-like and anticonvulsant effects of the AOE are due to GABAergic participation, whereas the antidepressant-like effects of the AOE are due to the noradrenergic system. The noradrenergic and GABAergic systems are involved in the anxiolytic-like actions of DHS. Full article

(This article belongs to the Special Issue Neuropharmacology of Plant Extracts and Their Active Compounds)

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12 pages, 2987 KiB

Open AccessArticle

Tocotrienol-Rich Fraction Ameliorates the Aluminium Chloride-Induced Neurovascular Dysfunction-Associated Vascular Dementia in Rats

by Sohrab A. Shaikh and Arunachalam Muthuraman

Pharmaceuticals 2023, 16(6), 828; https://doi.org/10.3390/ph16060828 - 1 Jun 2023

Cited by 3 | Viewed by 2295

Abstract

Neurovascular dysfunction leads to the second most common type of dementia, i.e., vascular dementia (VaD). Toxic metals, such as aluminium, increase the risk of neurovascular dysfunction-associated VaD. Hence, we hypothesized that a natural antioxidant derived from palm oil, i.e., tocotrienol-rich fraction (TRF), can attenuate the aluminium chloride (AlCl₃)-induced VaD in rats. Rats were induced with AlCl₃ (150 mg/kg) intraperitoneally for seven days followed by TRF treatment for twenty-one days. The elevated plus maze test was performed for memory assessment. Serum nitrite and plasma myeloperoxidase (MPO) levels were measured as biomarkers for endothelial dysfunction and small vessel disease determination. Thiobarbituric acid reactive substance (TBARS) was determined as brain oxidative stress marker. Platelet-derived growth factor-C (PDGF-C) expression in the hippocampus was identified using immunohistochemistry for detecting the neovascularisation process. AlCl₃ showed a significant decrease in memory and serum nitrite levels, while MPO and TBARS levels were increased; moreover, PDGF-C was not expressed in the hippocampus. However, TRF treatment significantly improved memory, increased serum nitrite, decreased MPO and TBARS, and expressed PDGF-C in hippocampus. Thus, the results imply that TRF reduces brain oxidative stress, improves endothelial function, facilitates hippocampus PDGF-C expression for neovascularisation process, protects neurons, and improves memory in neurovascular dysfunction-associated VaD rats. Full article

(This article belongs to the Special Issue Neuropharmacology of Plant Extracts and Their Active Compounds)

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33 pages, 2059 KiB

Open AccessReview

Hawaiian Plants with Beneficial Effects on Sleep, Anxiety, and Mood, etc.

by Pornphimon Meesakul, Tyler Shea, Shi Xuan Wong, Yutaka Kuroki and Shugeng Cao

Pharmaceuticals 2023, 16(9), 1228; https://doi.org/10.3390/ph16091228 - 30 Aug 2023

Cited by 7 | Viewed by 5776

Abstract

Diverse chemical messengers are responsible for maintaining homeostasis in the human body, for example, hormones and neurotransmitters. Various Hawaiian plant species produce compounds that exert effects on these messengers and the systems of which they are a part. The main purpose of this review article is to evaluate the potential effects of Hawaiian plants on reducing pain and anxiety and improving sleep and mood. A comprehensive literature search was conducted in SciFinder, PubMed, Science Direct, Scopus, Google Scholar, and Scientific Information Database between 2019 and 2023 to identify related articles. Results indicate that several Hawaiian plant species, such as M. citrifolia and P. methysticum, have medicinal properties associated with these effects. These plants have been used in traditional Hawaiian cultural practices for centuries, suggesting their potential to benefit human health and well-being. This review presents a comprehensive analysis of the available evidence concerning the potential impacts of Hawaiian plants on sleep, anxiety, mood, and pain. Full article

(This article belongs to the Special Issue Neuropharmacology of Plant Extracts and Their Active Compounds)

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24 pages, 11517 KiB

Open AccessSystematic Review

Neuroendocrine Biomarkers of Herbal Medicine for Major Depressive Disorder: A Systematic Review and Meta-Analysis

by Hye-Bin Seung, Hui-Ju Kwon, Chan-Young Kwon and Sang-Ho Kim

Pharmaceuticals 2023, 16(8), 1176; https://doi.org/10.3390/ph16081176 - 18 Aug 2023

Cited by 1 | Viewed by 1952

Abstract

Major depressive disorder (MDD) is a medical condition involving persistent sadness and loss of interest; however, conventional treatments with antidepressants and cognitive behavioral therapy have limitations. Based on the pathogenesis of MDD, treatments using herbal medicines (HM) have been identified in animal studies. We conducted a systematic review of clinical studies to identify neurobiological outcomes and evaluate the effectiveness of HM in treating MDD. A meta-analysis was performed by searching nine databases from their inception until 12 September 2022, including 31 randomized controlled trials with 3133 participants, to examine the effects of HM on MDD using neurobiological biomarkers and a depression questionnaire scale. Quality assessment was performed using a risk of bias tool. Compared to antidepressants alone, HM combined with an antidepressant significantly increased concentrations of serotonin (SMD = 1.96, 95% CI: 1.24–2.68, p < 0.00001, I² = 97%), brain-derived neurotrophic factor (SMD = 1.38, 95% CI: 0.92–1.83, p < 0.00001, I² = 91%), and nerve growth factors (SMD = 2.38, 95% CI: 0.67–4.10, p = 0.006, I² = 96%), and decreased cortisol concentrations (SMD = −3.78, 95% CI: −4.71 to −2.86, p < 0.00001, I² = 87%). Although HM or HM with an antidepressant benefits MDD treatment through improving neuroendocrine factors, these findings should be interpreted with caution because of the low methodological quality and clinical heterogeneity of the included studies. Full article

(This article belongs to the Special Issue Neuropharmacology of Plant Extracts and Their Active Compounds)

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