Journal of Herbmed Pharmacology
Volume:13 Issue: 4, Oct 2024

Davana (Artemisia pallens Wall. ex DC) is a well-known and precious essential oil-bearing plant under the family Compositae (Asteraceae). It is an erectly grown herbaceous plant exclusively cultivated as a short-term crop in south India during winter. It is distributed in the northern hemisphere in subtropical Africa, South Africa, West America, and South America; however, it is indigenous to southern India. The yearly productivity of davana oil typically falls between 8 to 10 tones. Davana oil is mainly used to flavor pastries, cakes, tobacco, and some beverages. It consists of diverse phyto-molecules and is an important and unique commodity in the fragrance, flavor, and liquor industries. It has excellent biological potential and contains volatile and nonvolatile constituents such as terpenoids, flavonoids, and alkaloids, which have high pharmacological values. Several investigations have focused on validating the importance of chemical constituents and the biological efficacy of essential oils and various extracts in multiple industries. The review focuses on the complete agronomic practices, botany, breeding, biotechnology, and chemistry of davana essential oil (DEO), viz, volatile and nonvolatile constituents, phytomedicinal and pharmacological properties, which may help researchers achieve their future goals for approaching its industrial or commercial viability as a natural product ingredient.

Depression is characterized by symptoms such as insomnia, change in appetite and body weight, impaired concentration, lethargy, agitation, psychomotor retardation, anhedonia, feelings of worthlessness, and suicidal thoughts. Various methods have been applied to assess the efficacy of antidepressants and associated molecular processes. However, guidance on the selection of methods for antidepressant testing is still lacking. This article provides a comprehensive review focusing on animal models of depression and the behavioral and molecular changes. A literature search was conducted on platforms, such as PubMed, Google Scholar, Scopus, and Science Direct to find relevant articles. This review found that chronic unpredictable mild stress might be the best and most commonly used model for inducing depression and simulating human depressive states in animals. This model employs a naturalistic approach to expose animals to unpredictable stressors that disrupt homeostasis and cause somatic, physiological, neurobiological, and biochemical disorders and behaviors. The forced swim test (FST) is the most frequently used simple behavioral testing method that is consistent with antidepressant effects, reduces immobility time, and serves as the leading indicator of antidepressant effectiveness. The most commonly observed molecular changes are those related to the levels of monoamine neurotransmitters, such as 5-hydroxytryptamine, dopamine, norepinephrine, and brain-derived neurotrophic factor (BDNF), which are the main etiological contributors to depression. The findings from this review will contribute to ongoing efforts to discover and develop drug candidates for the treatment of depression.

The Ficus genus is universally recognized for its medicinal properties. This article aims to comprehensively review the antioxidant potential and pharmacological properties of some key Ficus species within the genus, regarding their natural antioxidants and pharmacological properties. An extensive literature search was conducted across multiple databases using keywords such as Ficus species, antioxidant activity, and pharmacological applications. This review revealed notable differences in antioxidant capacity among the selected Ficus species. Comparative studies within the review indicated that factors such as geographical location, extraction method, and specific part of the plant used, significantly influenced the antioxidant activity and phytochemical content. Among these, F. benghalensis, F. carica, and F. krishnae exhibited the highest antioxidant capacities. Regarding overall pharmacological effectiveness, the species that out were F. religiosa, F. carica, and F. elastica. In sum, Ficus species emerge as a promising source of natural antioxidants with substantial pharmacological potential. Future research should focus on clinical trials to validate their medicinal uses, exploring the mechanism of actions, and potential applications in developing novel therapeutic agents.

 Environmental temperature conditions might influence the composition of secondary metabolites in certain medicinal plants. This study aimed to examine how some of the phytochemicals and anticancer properties of Carpobrotus edulis may be impacted by temperature conditions.

 The plant specimens were kept in growth chambers at 15/10 °C and 45/35 °C (day/night), and harvested at 48-hour intervals (48, 96, and 144 hours). Control conditions were maintained at 25/15 °C. Standard phytochemical colour tests were used to determine the presence of eight phytochemicals. The anticancer activity against cervical cancer cell lines was determined using cell viability assay, cell morphology, Hoechst staining, and wound healing assays.

 The phytochemical screening showed the presence of all tested phytochemicals (phenolics, flavonoids, terpenoids, saponins, tannins, steroids, and cardiac glycosides) in all treatments except for saponins in the 96- and 144-hour temperature treatments. A noteworthy IC50 value of 284.9 µg/mL was determined from the methanolic leaf extract exposed to high temperatures for 144 hours against cervical cancer. Treatment with this extract suggested changes in cancer cell morphology, signs of apoptosis, and cell migration inhibition.

 The preliminary results obtained suggest that the C. edulis methanolic extract has potential anticancer properties against cervical cancer. These observations may have implications for the indigenous plant use in treating various ailments and broaden the type of anticancer research involving this plant.

 Momordica cardiospermoides represents an inexhaustible source of natural products. We examined the acetone and methanolic extracts of M. cardiospermoides leaves’ phytochemical composition, antioxidant activities, and anti-metastatic properties in MDA-MB-231 cells.

 The aluminium chloride and Folin-Ciocalteu methods were employed to determine the extracts’ phytochemical contents. Assessment of antioxidant activities employed the 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. The extracts were further characterized with ultra-high-performance liquid chromatography (UHPLC). The cell count and viability kit were utilized to assess viability in HEK-293 and MDA-MB-231 cells. The occurrence of cell death was determined by the annexin V and dead cell assay. The methanolic extract was assessed against cell adhesion and migration using the cell-extracellular matrix and wound healing assays. The effects of the methanolic extract on tissue inhibitors, including metalloproteinase-1 (TIMP-1), matrix metalloproteinases-2 (MMP-2), and -9 (MMP-9) were determined by the human angiogenesis antibody array kit and Western blot analysis.

 The acetone extract had higher antioxidant activity and total contents than the methanolic extract. UHPLC revealed abundant luteolin, luteoloside, quercetin, stearidonic acid, and salicylamide in the acetone extract, and luteolin, astragalin, and trigonelline in the methanolic extract. The methanolic extract was selectively cytotoxic towards MDA-MB-231 cells while the acetone extract was significantly cytotoxic in both cell lines. Apoptosis was induced by the methanolic extract and the acetone extract induced significant necrosis. The methanolic extract suppressed migration by significantly inhibiting wound closure and inhibited cell adhesion. MMP-2 and MMP-9 were significantly downregulated and TIMP-1 was upregulated.

 The methanolic extract M. cardiospermoides possesses anti-metastatic activity.

 Thymus vulgaris is a plant used in Cameroon to alleviate and treat hangover symptoms. This study was conducted to assess the anxiolytic, memory-improving, hepatoprotective, and antioxidant effects of T. vulgaris on alcohol withdrawal syndrome.

 In this preclinical study 42 mice were grouped into seven equal sets of normal control, negative control, positive control (piracetam; 200 mg/kg), and test (T. vulgaris; 25, 50, 100, or 200 mg/kg) groups. All mice (except those of the normal control) were administered ethanol by gavage once daily for 28 days. After alcohol withdrawal, behavioral assessments (elevated plus maze, Y-maze, and open field) were performed from day 29 to day 31, one hour following appropriate treatments. Mice were euthanized on day 32 and the brains and the livers were used for histopathological assessment and oxidative stress parameters evaluation.

 In the elevated plus maze test, T. vulgaris at 100 and 200 mg/kg significantly (P < 0.001) increased the number of entries and the time spent in the open arms. The plant extract (200 mg/kg) significantly (P < 0.001) increased the spontaneous alternation percentage in the Y maze. T. vulgaris administration decreased malondialdehyde (MDA) and nitric oxide (NO) in the brain and liver and increased glutathione (GSH) and catalase (CAT). The plant extract reduced the neuronal degeneration and hepatocyte damage induced by chronic alcohol administration.

 T. vulgaris had anxiolytic, memory-enhancing, and hepatoprotective properties against alcohol toxicity. These results may justify the use of thyme in traditional pharmacopeia in the management of alcohol use disorders (AUDs).

 Type 2 diabetes mellitus (T2DM) affects millions of people worldwide, highlighting the importance of dietary interventions. Flaxseed (Linum usitatissimum L.) has shown promise in treating chronic metabolic diseases. This study investigates the therapeutic potential of flaxseed as an antidiabetic agent and its protective effect on cardiovascular diseases.

 Rats were randomly divided into five groups: normal fed with drug carrier group (N), diabetes with drug carrier group (D), diabetes with metformin (M) group (D+M), and diabetes with flaxseed extract doses of 100 and 200 mg/kg (D+F1 and D+F2) groups. The diabetic rat model was established by administration of drinking water containing 25% fructose and a single intraperitoneal injection of 100 mg/kg alloxan. After a six-week intervention, the rats were sacrificed to assess the antidiabetic and cardiovascular effects.

 The doses of 100 and 200 mg/kg flaxseed extract significantly reduced body weight and fasting glucose levels and increased insulin sensitivity index (KITT) compared to the diabetes group (P<0.05). In addition, histological analysis showed a significant improvement and increase in pancreatic beta cells in the treatment group compared to the diabetes group (P<0.05). Flaxseed extract doses of 100 and 200 mg/kg significantly reduced weight gain and insulin resistance, contributing to decreased arterial stiffness and atherogenic index compared to the diabetic group (P<0.05). The hypoglycemic effect suggested a dose-dependent response.

 Flaxseed extract regulates blood glucose levels probably by enhancing insulin sensitivity and revitalizing damaged pancreatic beta cells. It mitigates cardiovascular risk, by reducing arterial stiffness and atherogenicity.

 The extract of Solanum xanthocarpum fruit has antidiabetic activity. This research aims to formulate nanoliposomes containing ethyl acetate extracts of S. xanthocarpum selected from multilevel extraction, evaluate their physical stability and antidiabetic activity, and compare them with the extract.

 The extracts were prepared using n-hexane, ethyl acetate, ethanol, and water as solvents, and their antidiabetic activities were evaluated to select the extract most effective in lowering blood sugar levels in rats. That extract was formulated into three nanoliposomes using varying amounts of phospholipid, cholesterol, and Span 60, i.e., F1 (40 mmol), F2 (50 mmol), and F3 (60 mmol). Various sonication times ranging from 10 to 30 minutes were evaluated for particle size, entrapment efficiency, and physical stability. The selected formulations were evaluated for antidiabetic activity.

 The ethyl acetate extract showed the highest decrease in glucose in rats and was selected for nanoliposome formulation. The nanoliposomes obtained were physically stable at low temperatures for 12 weeks. F2 had the smallest particle size (143.97 nm) and the greatest entrapment efficiency (92.981% ± 0.35%) with a sonication time of 30 minutes and was significantly different from F1 and F3 (P<0.05). The highest percentage reduction in blood sugar levels was with F2 at 74.57% and significantly differed (P<0.05) from the ethyl acetate extract of S. xanthocarpum at 73.98% and the positive control rat group.

 The results show the potential uses of the prepared nanoparticles, especially the F2 formulation, as an antidiabetic formula.

 Tinospora cordifolia (TC) possesses antioxidative properties and has been shown to improve cognition. In this study, the effects of TC were investigated on prenatal vibratory stress, maternal separation-induced amygdala plasticity, and memory retention in pregnant rats and their neonates.

 Four experimental animal groups of pregnant Wistar rats were employed in this research, including normal & vehicle controls, the stressed group, which received 3 hours of vibratory stress/day, and the TC-treated group, which received 6 mg/kg TC before vibratory stress. The neonates born to these mothers were then subjected to maternal separation, followed by postnatal TC treatment. After 6 weeks, the animals were assessed to evaluate memory retention, serum cortisol levels, and neuronal structural changes in the amygdala.

 Neonates exposed to prenatal vibratory stress and maternal separation entered the dark compartment more quickly during the retention test (P<0.001), indicating reduced memory retention. In contrast, the TC-treated groups showed longer latencies (P<0.001), suggesting improved memory retention. The TC-treated mothers and neonates had longer dendrites with more branching points and intersections (P<0.001). However, these dendrites underwent pruning, indicating a complex structural response to stress and TC treatment.

 The results indicate that TC exerts neuroprotective effects against prenatal vibratory stress and maternal separation and aids memory retrieval in rats by restoring amygdala neuronal damage.

Despite the traditional use of Cucurbita pepo seed in pregnancy, its effects on female reproduction remain scarce. This study evaluated the impacts of n-hexane, dichloromethane (DCM), and aqueous ethanol extracts of C. pepo seed on the cyclicity and reproductive hormones of female Wistar rats.

Ten groups of four rats received seed extracts or tween 80 orally for 21 days: A (control)= 0.5 mL tween 80 (vehicle); B, C, & D= 142.86, 285.71, and 428.57 mg/kg nHE; E, F, & G= 142.86, 285.71, 428.57 mg/kg of DCM; and H, I, & J= 142.86, 285.71, 428.57 mg/kg of aqueous ethanol extracts, respectively. Vaginal cytology monitored the estrous cycle daily, and blood samples were obtained for follicle-stimulating hormone (FSH), luteinizing hormone (LH), estrogen, and progesterone at various oestrus cycle phases.

Compared to the control, the estrous cycle phases did not change significantly (P>0.05). FSH levels significantly increased (P<0.05) with DCM and aqueous ethanol extracts of C. pepo seed during proestrus and estrus phases compared to the control. A significant (P<0.05) increase in LH was observed with n-hexane, DCM, and aqueous ethanol extracts during all estrous cycle phases compared to the control. All extracts significantly increased estrogen levels (P<0.05) during all phases. DCM and aqueous ethanol extracts reduced substantially the estrus-phase progesterone.

Cucurbita pepo may stimulate the hypothalamic-pituitary-gonadal axis in female reproduction. Further studies should be conducted using various phytoestrogen compounds to gain useful knowledge about the effectiveness, safety, and long-term effects of C. pepo seed extracts in regulating hormonal balance.

 Pluchea indica is known to have diverse pharmacological properties, including anti-inflammatory, antioxidant, antimicrobial, and anticancer activities. However, there is a pressing need to thoroughly investigate the molecular interactions between P. indica compounds and peroxisome proliferator-activated receptor gamma (PPARG). This study aimed to elucidate the molecular mechanisms behind P. indica and PPARG, and its potential implications for diabetes mellitus.

 The computational investigation employed Pharmacological Network pharmacology, homology modeling, deep learning docking, and molecular dynamics to explore the active compounds and targets within P. indica against the PPARG.

 Three active compounds were identified namely pinoresinol, syringaresinol, and plucheoside A, all of which complied with the Lipinski rule of five. The deep learning-based pose scores were determined as follows: Pinoresinol 0.55, syringaresinol 0.32, and plucheoside A 0.44. Additionally, protein-protein interactions were observed with PPARG and associated with the PPAR signaling pathway. Molecular dynamics simulation analysis showed the stability of the three compounds over a 100 ns period. Free energy calculations using Molecular Mechanics-Generalized Born and Surface Area (MM-GBSA) yielded ΔG values of -44.39 kcal/mol, -51.83 kcal/mol, and -40.27 kcal/mol for pinoresinol, syringaresinol, and plucheoside A, respectively.

 Pluchea indica might be developed to treat various diseases, particularly those involving the PPARG signaling pathway. It suggests the possibility of being developed as a focused medication for diabetes.

 Alpinia galanga (L.) Willd is a rhizomatous, recurrent herb used to treat numerous diseases, including cancer. This study examines the efficiency of the different parts of A. galanga for their phytochemical, antioxidant, and anti-cancer properties.

 The powdered leaf, stem, and rhizome of A. galanga were extracted using hexane, ethyl acetate and methanol; the phytochemical compositions of the extracts were characterized using high performance liquid chromatography (HPLC) and gas chromatography-mass spectroscopy (GC-MS). Their antioxidant potentials were evaluated using different assays, including 2,2-Diphenyl-1picrylhydrazil (DPPH), 2-Azino-bis-3-ethylbenzothiazoline-6-sulphonic acid (ABTS), Superoxide anion (O2-), Hydroxyl radical (OH), and Phosphomolybdenum assays. The in vitro anticancer activity was studied using the 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay. Comet assay was used to determine the level of DNA damage. Inductions of morphological alterations were studied using the AO/Et-Br dual staining method. The ELISA kits were used to measure caspase activities.

 The cytotoxicity results showed that the various extracts had inhibitory and cytotoxic effects on cancer cell lines. The leaf hexane (LH) extract of A. galanga induced DNA damage with prominent increased tail length and tail moment followed by the induction of apoptotic cells and up-regulation of the caspase activities. HPLC and GC-MS analysis allowed the identification of bioactive compounds, recognized as apoptotic inducers in human cancer cells by activating caspase-dependent pathways.

 This work reports for the first time the effect of LH extract of A. galanga in triggering apoptosis in A-549 and HeLa cells through the upregulation of caspase-8 and caspase-3 activities.

 Sarcopenia is an inflammatory disease caused by a disruption of muscle homeostasis. Lonicera caerulea L. (Haskap berry) (HB) extract and omega-3 (ω−3) possess antioxidant and anti-inflammatory activities. This study assesses the potential ameliorating effects of HB extract and ω−3 supplementation on dexamethasone (DEXA)-induced sarcopenia.

 Rats were divided into five groups; the negative control group was injected with saline (i.p.); groups 2, 3, 4, and 5 were injected with DEXA (2 mg/kg/d, i.p.); groups 3 and 4 also received 400 mg/kg/d and 100 mg/kg/d of HB extract and ω−3, respectively, while group 5 received both treatments daily for 21 days. The ameliorative effects of treatments were investigated by measuring lysosomal proteolytic enzyme cathepsin activity, phosphatidylinositol 3 kinase (PI3K) activity, nuclear factor kappa beta (NF-κB) level, and heme oxygenase-1 (HO-1) activity. The gene expression levels of muscle ring-finger protein (MuRF) and forkhead box O (FOXO) transcription factor were also evaluated. Biochemical and histological examinations were done on muscle tissues.

 DEXA caused a significant elevation (P<0.05) in NF-κβ level and cathepsin activity in muscle tissue. Also, it significantly upregulated the muscle atrophy markers. Meanwhile, PI3K and HO-1 activities were significantly reduced. HB extract and ω−3 administration significantly (P≤0.05) reversed these effects and downregulated the mRNA expression levels of MuRF and FOXO. Also, the histopathological examination confirmed these results.

 The current study proved the ameliorative effects of HB extract and ω−3 on sarcopenia parameters. Therefore, they might be potential therapeutic agents for myopathy/sarcopenia.

 Diabetes mellitus (DM) and Alzheimer’s disease (AD) are two highly linked disorders due to their association with the aging population. Several studies have reported the beneficial effects of diosgenin and pterostilbene in treating neurodegenerative diseases. This study aimed to investigate the neuroprotective mechanisms of diosgenin and pterostilbene through molecular docking and dynamics studies and assess their pharmacokinetic parameters.

 To understand the link between diabetes and AD, molecular docking of the natural ligands diosgenin and pterostilbene against the specific targets of AD, including β-secretase, glycogen synthetase kinase beta (GSK-3β), gamma-secretase, tumor necrosis factor-alpha (TNF-ɑ), and interleukin-6 (IL-6) was done to find out their binding affinities to explain the molecular mechanisms involved in their neuroprotection. Further molecular dynamics studies and binding energy calculations for the ligands with GSK-3β and β-secretase were carried out to confirm their docking activities. Additionally, pharmacokinetic analysis of these two phytoconstituents was performed by the SWISSADME server.

 Molecular docking and dynamics studies revealed the good docking activity of diosgenin and pterostilbene with the selected targets. Further, the two phytoconstituents revealed suitable pharmacokinetic parameters along with blood-brain barrier permeability, confirming their druggable nature.

 This research identified multiple neuroprotective pathways of diosgenin and pterostilbene that might be significant for treating diabetes-associated Alzheimer’s disease.

 Wild species of the genus Allium have high potential for use as medicine due to their essential secondary metabolites with antioxidant activity. This study explored the antioxidant, antibacterial, and α-glucosidase inhibition activities of three Allium species: Allium tripedale, Allium hooshidaryae, and Allium stipitatum.

 The antioxidant potentials of the plant methanol extracts were evaluated using the ferric reducing antioxidant power (FRAP) and the 2,2-diphenyl-1picrylhydrazil (DPPH) radical scavenging test. Total phenolic content (TPC), total flavonoid content (TFC) and α-glucosidase inhibition were also evaluated. Antibacterial assessments were done employing disk diffusion and microdilution methods to determine inhibition zone and minimum inhibitory concentration (MIC), respectively against Staphylococcus aureus, Bacillus subtilis, Escherichia coli, and Pseudomonas aeruginosa.

 Allium hooshidaryae displayed high TPC (70.24 ± 0.0039 mg gallic acid equivalent/g extract), while A. tripedale had the highest TFC (87 ± 0.013 mg Quercetin equivalent/g extract). A. hooshidaryae showed superior antioxidant capacity (DPPH IC50: 724.4 ± 0.31 µg/mL; FRAP: 36.87 mg ascorbic acid equivalent/g extract) and stronger α-glucosidase inhibition (IC50 = 2.59 mg/mL vs. 4.33 mg/mL for A. tripedale and 6.41 mg/mL for A. stipitatum). Qualitative tests confirmed phenolic, flavonoid, and glycoside compounds in all three species. A. stipitatum uniquely contained saponin and tannin. A. hooshidaryae and A. stipitatum inhibited the bacterial strains effectively, especially at the higher concentration (400 µg/mL). A. stipitatum showed inhibition against all strains, particularly against S. aureus (MIC: 12.5 µg/mL).

 This study highlights the antidiabetic and antibacterial potential of three Allium species, emphasizing their values as rich sources of bioactive compounds.