Journal of Advanced Pharmaceutical Technology & Research最新文献

Neurodegenerative diseases (NDs) are pathological conditions initiated by the loss of neuronal cell structure and the progressive decline in function caused by prolonged neuroinflammation. Postmenopausal women are at a high risk of experiencing NDs due to estrogen deficiency in their bodies, necessitating the administration of phytoestrogens as a replacement for estrogen in the body. One alternative therapy is administering phytoestrogens, estrogen-like substances from plants, which can be obtained from Marsilea crenata C. Presl. leaves. The purpose of this study was to determine whether administration of the n-butanol fraction (BF) and water fraction (WF) of M. crenata leaves could increase locomotor activity in rotenone-induced zebrafish. Treatment was given to each group of zebrafish with BF and WF at doses of 2.5; 5; 10; and 20 ppm to determine the locomotor activity. Then an analysis was carried out by looking at each movement of the zebrafish swimming for 1 min at the time of observation on days 0, 7, 14, 21, and 28. The result showed that BF and WF significantly increased the locomotor activity of zebrafish at the optimum dose of 20 ppm for BF and 5 ppm for WF compared to the negative control. This concludes that the polar fraction of M. crenata leaves is proven to have the potential to prevent ND progressivity.

Diabetes mellitus is a chronic condition defined by elevated blood sugar levels (hyperglycemia). This condition can lead to complications such as nephropathy, which is histologically shown with glomerulosclerosis. Glucomannan, a component of Amorphophallus muelleri, offers numerous health benefits, but its direct therapeutic effect on glomeruli remains uncertain. Male Wistar rats which were taken with random sampling (n = 30) were distributed into six distinct groups. All groups, excluding Group N, received 125 mg/kg BW single intraperitoneal dose of alloxan. Group N received a single dose of PBS 125 mg/kg BW. After 7 days, Group K + was induced with acarbose at a dose of 50 mg/70 kg BW (adjusted using a factor of 0.018) orally per day. Groups N and K - induced with 1% CMC Na at 0.2 mL/0.1 kg orally per day. While Group P1, P2, and P3 were orally given A. muelleri ethanolic extract orally per day at a dose of 100, 200, and 400 mg/kg BW. The following 50 days of treatment, the Wistar rats were euthanized, and their kidney was preserved for histological slides that were stained with hematoxylin and eosin. The oral administration of A. muelleri ethanolic extract in alloxan-induced diabetic rats led to a significant decrease in the average of glomerulosclerosis instances when compared to the K - group. The most effective dose was observed at 400 mg/kg BW per day. A. muelleri administration leads to a reduction in glomerulosclerosis occurrences, suggesting its potential as a therapeutic approach for reducing complications probability linked to hyperglycemia.

Small molecules are considered a source of novel medicines targeting carcinogenic intracellular pathways including epidermal growth factor receptor (EGFR) signaling. The main goal of the study is to assess whether LHT-17-19 could be considered an effective target molecule against EGFR-expressing tumor cells in silico, in vitro, and in vivo. This was an in vivo, ex vivo, and in vivo experimental study. LHT-17-19 affinity to EGFR's kinase domain was assessed by the ligand's molecular docking. EGFR-expressing Hs746T human gastric cancer cell culture and patient-derived organoid (PDO) model of EGFR-positive breast cancer (BC) were used for in vitro assessment of the molecule anticancer property. IC₅₀ and GI₅₀ indexes were estimated using MTT- and MTS-based tests, respectively. Anticancer activity of LHT-17-19 against EGFR-expressing mutant lung carcinoma was studied on patient-derived xenograft (PDX) model established in 10 humanized BALB/c male mice. Continuous variables were presented as a mean ± standard deviation. Intergroup differences were assessed by two-way t-test. Kaplan-Meier's curves were used for survival analysis. High affinity of LHT-17-19 for the EGFR kinase domain with dG score -7.9 kcal/mol, EDoc-5.45 kcal/mol, and Ki 101.24 uM was due to intermolecular π-σ bonds formation and the ligand intramolecular transformation. LHT-17-19 induced anti-EGFR-expressing gastric cancer cells cytotoxicity with IC₅₀ 0.32 µM (95% confidence interval [CI] 0.11-0.54 µM). The derivative inhibited growth of EGFR-expressing BC PDO with GI₅₀ 16.25 µM (95% CI 4.44-28.04 µM). 2 mg/kg LHT-17-19 intravenously daily during 7 days inhibited PDX tumor growth and metastatic activity, prolonged animals' survival, and eliminated EGFR-mutant lung cancer cells from residual tumor's node. LHT-17-19 may be considered a molecular platform for further search of promising molecules, EGFR-expressing cancer cell inhibitors.

Fish oils are good sources for essential fatty acids such as omega-3 and omega-6 fatty acids needed to human growth. Indonesia is rich in fish species and among this, red snapper fish (Lutjanus sp.) can be extracted to get red snapper fish oils (RSFOs). The aim of this study was to classify and discriminate RSFO from different origins using Fourier-transform infrared (FTIR) spectra and pattern recognition techniques. All of the RSFO's FTIR spectra were very similar. The FTIR vibrations showed the presence of triglycerides as the main composition in fish oils. Principal component analysis (PCA) could separate the RSFO according to sample origin. Supervised pattern recognition of partial least square-discriminant analysis (PLS-DA) and sparse PLS-DA (sPLS-DA) successfully discriminated and classified different Lutjanus species of fish oils obtained from different origins. The vibration of functional groups at 1711, 1653, 1745, and 3012 per cm were considered for their important contributions in discriminating of Lutjanus species (variable importance in projection, variable importance in the projection score >1). Fish oils obtained from the same species were classified into the same class indicating similar chemical compositions. Among the three pattern recognition techniques used, sPLS-DA offers the best model for the discrimination and classification of Lutjanus fish oils. It can be concluded that FTIR spectroscopy in combination with the pattern recognition technique is the potential to be used for of fish oil authentication to verify the quality of the fish oils. It can be further developed as a rapid and effective method for fish oil authentication.

Millions of bacteria present in the mouth cavity contribute to the challenging management of oral mucosa injury. On the other hand, Gracilaria spp. (red algae) is one of the widely cultivated algae that have a strong potential as a wound-healing agent for oral mucosa injury. This study aimed to investigate the wound-healing property of the red algae by observing its effect on polymorphonuclear (PMN), a neutrophil that is usually recruited during the initial wound healing. The extract was obtained through maceration and used as bioactive ingredient in gel preparation. Rattus norvegicus with incision wounds in the oral mucosa was used as the animal model. Our results revealed that rats treated with the red algae gel had significantly lower PMN on the injury site (P < 0.01) as observed on days 1, 3, and 5. Identification using gas chromatography-mass spectrometry showed that the extract was rich in hexadecenoic acid and glycerol. The brine shrimp lethality test suggested low cytotoxicity of this extract with LC₅₀ = 10694.93 mg/mL. In conclusion, the extract could be potentially used as bioactive ingredient in gel formulation for topical management of oral mucosa wounds. Further, research to confirm these findings is warranted.

The invasive plant, Sphagneticola trilobata (L.) J. F. Pruski, has been known for its bioactivities and used to synthesize gold nanoparticles (AuNPs). Nonetheless, previous research has not directly compared the effectiveness of the plant parts in producing the AuNPs. The objective of this study was to compare the effectiveness of the flower and leaf of S. trilobata in synthesizing AuNPs. S. trilobata leaves and flowers were separately extracted using distilled water at 60°C for 30 min. The leaf and flower extracts were mixed with the HAuCl. 3H₂O and heated to 60°C for 30 min to yield AuNPs-ALSt and AuNPs-AFSt, respectively. AuNPs were also prepared using trisodium citrate (Na₃C₆H₅O₇) as a control. The resultant AuNPs were characterized using an ultraviolet-visible spectrophotometer, particle size analyzer, and scanning electron microscope. Antioxidant activity was evaluated based on 1-diphenyl-2-picrylhydrazyl (DPPH) inhibition and anticancer activity- 3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide assay against MCF-7 cells. The AuNPs-ALSt and AuNPs-AFSt were revealed to have better stability and smaller particle diameters. AuNPs-ALSt and AuNPs-AFSt had average particle diameters of 11.86 ± 3.37 and 34.86 ± 23.56 nm, respectively. Agglomeration was predominantly observed in AuNPs synthesized using the flower or leaf extract as stipulated to be affected by the insufficient capping agent and intense hydrolytic reaction. AuNPs-AFSt had higher DPPH antioxidant activity than AuNPs-ALSt with half-maximal inhibitory concentrations of IC₅₀ 123.44 and 168.83 ppm, respectively. Both AuNPs-ALSt and AuNPs-AFSt could inhibit 80% growth of the MCF-7; however, at lower concentrations, inhibitory effects were more pronounced in AuNPs-AFSt. Aqueous extracts of S. trilobata flowers and leaves could be used to synthesize AuNPs, whereas the former yielded AuNPs with higher biological activities.

Globally, an estimated 50 million people are affected by epilepsy, a persistent, noncommunicable neurological ailment. Quercetin (QR) is a prevalent flavonoid substance extensively dispersed throughout agricultural life. In a pilocarpine (PILO)-induced epilepsy model in mice, this investigation aimed to determine whether QR has an antiepileptic effect and explore its putative mechanism of action. Fifty mice were allocated into seven groups, with six in every group. The first group received physiological saline, the second group was given diazepam (1 mg/kg), and four groups were administered QR at 50, 100, 150, and 200 mg/kg, respectively. The seventh group (the induction group) received normal saline. After 30 min, all groups were injected intraperitoneally with PILO. The impact of QR on motor coordination was assessed using the rotarod test, while measures such as latency to first seizure, generalized tonic-clonic seizures (GTCS), number of convulsions, and mortality were recorded. Serum samples were collected through the retro-orbital route to measure prostaglandin E2 (PGE2) and interleukin 1 beta (IL-1β) levels. QR showed no significant difference in motor impairment, but increased duration until the initial seizure occurred and declined the mortality rate, duration of GTCS, and incidence of convulsions. All doses of QR significantly reduced PGE2 levels (P ≤ 0.05). However, QR's effect on IL-1β reduction was statistically insignificant (P > 0.05). QR's capacity to inhibit PILO-induced epilepsy by decreasing IL-1 and PGE2 levels is supported by this study. The results of this work indicate that QR could have a function to treat acute epilepsy.

Leaves of Annona muricata have medicinal potential which has gained attention from researchers around the world. This study has an objective to screen the antioxidant and cytotoxicity of ethyl acetate extract from A. muricata leaves and its fraction. The fine powder of A. muricata was macerated in methanol and further partitioned using two different solvents, namely n-hexane and ethyl acetate. In this article, we reported the screening results for ethyl acetate extract. Fractionation was then performed on the extract by means of column chromatography by gradient elution resulting in five combined fractions. Brine shrimp lethality test and 1-diphenyl-2-pycrilhidrazil (DPPH) assays were employed to evaluate the cytotoxicity and antioxidant of the extract, respectively. Characterization using gas chromatography-mass spectroscopy (GC-MS) was then conducted. The cytotoxicity of the samples was indicated by median lethal concentration₅₀ values ranging from 28.84 to 1023.3 ppm. As for the antioxidant activity, the DPPH median inhibitory concentration₅₀ values ranged from 4.12 to 180.66 ppm. GC-MS analysis on the most bioactive fraction revealed the predominating phytochemical contents of neophytadiene, palmitic acid, and phytol. In conclusion, the fraction of ethyl acetate extract from A. muricata leaves could potentially act as a strong antioxidant and moderate cytotoxic agent.

In this study, we delved into the hippocampal region to understand the effects of adipose stem cells (ADSCs) and rosemary extract (RE). Our main objective was to explore how these substances influence spatial memory, neurotrophins, and changes in antioxidant enzymes. Moreover, we meticulously investigated the impact of dopamine deficiency, a notable characteristic linked with Parkinson's disease (PD), on memory impairment. This study comprised five groups of Wistar rats - all male, all selected randomly. We labeled two of these gatherings "lesion" (L) and "sham" (SH). Each got injections in the bilateral form with 6 μg - one group getting saline, while another got 6-OHDA. From couple weeks before the neurotoxin injection to 8 weeks later on, our lesion cohort was treated with rosemary at a dosage rate of 50 mg/kg body weight - let's call it RE for simplicity sake. Moreover, there is also this other lot, designated as cell-transplanted lesion group or catchy exercise (CE) as we prefer to interpret them; they had cell transplants conducted exactly 7 days after receiving their respective injections. Bringing up the rear, we got a group treated with both cell transplant and rosemary (CE+R). We performed spatial memory tests at 4 weeks, then again at 8. At the end of eighth week, the brains were extracted for q-PCR, enzymatic and immunohistochemical studies. Turning our gaze toward a comparison between the CE+R and CE groups versus the L group, we spot an intriguing drop in escape latency time. There is also more time spent in quadrants. Digging deeper into this matter, the CE+R bunch unveiled a clear surge when it comes to the expression of four genes, namely NGF, BDNF, NT3, and NT4! This was notable especially while comparing with both R and even other fellows from its very own broader group - CE. In a bit complex bit related to enzyme activity now, there is some good news as well for those in favor of potent antioxidants such as GPx or SOD. CE + R group, showed a significant increase of GPX and SOD enzymes, compared to the SH and L groups, and a significant decrease of MDA activity as compared to other treated groups. A significant decrease of escape latency and increase of time in quadrant were observed in the CE+R and CE groups compared to L group. What's more, the levels of MDA in the CE+R group plummeted significantly when set up against the SH group. Wrapping things up, a definite downscale was observed in the density of GFAP-positive cells throughout different regions located within the hippocampus; this decline presented itself not solely in treatment groups but gripped onto those falling under SH as well, especially when compared to its comrade - the L group. Using ADSCs and taking RE orally have shown promising results in improving memory issues linked with PD.

We developed innovative self-amplifying mRNA (sa-mRNA) vaccine based on the derivative of S and Nsp3 proteins, which are considered crucial adhering to human host cells. We performed B-cell, Major histocompatibility complex (MHC) I, and II epitope which were merged with the KK and GPGPG linker. We also incorporated 5' cap sequence, Kozak sequence, replicase sequence, 3'/5' UTR, and poly A tail within the vaccine structure. The vaccine structure was subsequently docked and run the molecular dynamic simulation with TLR7 molecules. As the results of immune response simulation, the immune response was accelerated drastically up to >10-fold for immunoglobulin, interferon-γ, interleukin-2, immunoglobulin M (IgM) + immunoglobulin G (IgG) isotype, IgM isotype, and IgG1 isotype in secondary and tertiary dose, whereas natural killer cells, macrophages, and dendritic cells showed relatively high concentrations after the first dose. As our finding, the IgM + IgG, IgG1 + IgG2, and IgM level (induced by sa-mRNA vaccine) ensued three times with two-fold increase in days 25, and 50, then decreased after days 70-150. However, 150-350 days demonstrated constantly in the range of 20,000-21,000.