Journal of Pharmaceutical Analysis

Ginsenoside Rc: A potential intervention agent for metabolic syndrome

Zhengjie Lu, Tongyun Mao, Kaiqi Chen, Longxin Chai, Yongguo Dai, Kexin Liu

2023, 13(12): 1375-1387. doi: 10.1016/j.jpha.2023.08.013

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Abstract:
Ginsenoside Rc, a dammarane-type tetracyclic triterpenoid saponin primarily derived from Panax ginseng, has garnered significant attention due to its diverse pharmacological properties. This review outlined the sources, putative biosynthetic pathways, extraction, and quantification techniques, as well as the pharmacokinetic properties of ginsenoside Rc. Furthermore, this study explored the pharmacological effects of ginsenoside Rc against metabolic syndrome (MetS) across various phenotypes including obesity, diabetes, atherosclerosis, non-alcoholic fatty liver disease, and osteoarthritis. It also highlighted the impact of ginsenoside Rc on multiple associated signaling molecules. In conclusion, the anti-MetS effect of ginsenoside Rc is characterized by its influence on multiple organs, multiple targets, and multiple ways. Although clinical investigations regarding the effects of ginsenoside Rc on MetS are limited, its proven safety and tolerability suggest its potential as an effective treatment option.

Recent trends of machine learning applied to multi-source data of medicinal plants

Yanying Zhang, Yuanzhong Wang

2023, 13(12): 1388-1407. doi: 10.1016/j.jpha.2023.07.012

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In traditional medicine and ethnomedicine, medicinal plants have long been recognized as the basis for materials in therapeutic applications worldwide. In particular, the remarkable curative effect of traditional Chinese medicine during corona virus disease 2019 (COVID-19) pandemic has attracted extensive attention globally. Medicinal plants have, therefore, become increasingly popular among the public. However, with increasing demand for and profit with medicinal plants, commercial fraudulent events such as adulteration or counterfeits sometimes occur, which poses a serious threat to the clinical outcomes and interests of consumers. With rapid advances in artificial intelligence, machine learning can be used to mine information on various medicinal plants to establish an ideal resource database. We herein present a review that mainly introduces common machine learning algorithms and discusses their application in multi-source data analysis of medicinal plants. The combination of machine learning algorithms and multi-source data analysis facilitates a comprehensive analysis and aids in the effective evaluation of the quality of medicinal plants. The findings of this review provide new possibilities for promoting the development and utilization of medicinal plants.

Anti-inflammatory natural products modulate interleukins and their related signaling markers in inflammatory bowel disease: A systematic review

Gopalsamy Rajiv Gandhi, Thiruchenduran Mohana, Kumaraswamy Athesh, Varghese Edwin Hillary, Alan Bruno Silva Vasconcelos, Mariana Nobre Farias de Franca, Monalisa Martins Montalvão, Stanislaus Antony Ceasar, Gnanasekaran Jothi, Gurunagarajan Sridharan, Ricardo Queiroz Gurgel, Baojun Xu

2023, 13(12): 1408-1428. doi: 10.1016/j.jpha.2023.09.012

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This review aims to identify in vivo studies investigating the potential of plant substances and their natural molecules in managing inflammatory bowel disease (IBD). Specifically, the objective is to examine the impact of these substances on interleukins and other key inflammatory signaling markers. Relevant articles published up to December 2022 were identified through a search of the PubMed, Scopus, Web of Science, and Embase databases. The search used keywords including “inflammatory bowel disease”, “medicinal plants”, “natural molecules”, “anti-inflammatory”, and “ulcerative colitis”, and identified 1,878 potentially relevant articles, of which 89 were included in this review after completion of the selection process. This study provides preclinical data on natural products (NPs) that can potentially treat IBD, including ulcerative colitis. The main actions of these NPs relate to their effects on nuclear factor kappa B (NF-κB), the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling pathway, the regulation of T helper 17/regulatory T cells balance, and oxidative stress. The ability of these NPs to inhibit intestinal inflammation appears to be dependent on lowering levels of the pro-inflammatory cytokines tumor necrosis factor-alpha (TNF-α), interleukin (IL)-1β, and IL-17, via the Jun N-terminal kinase (JNK)1, NF-κβ-p65, and STAT3 pathways. In addition, NPs were shown to reduce oxidative stress and the severity of ulcerative colitis, as well as increase the activity of antioxidant enzymes. These actions suggest that NPs represent a promising treatment for IBD, and potentially have greater efficacy and safety than current treatments.

Application of microfluidic technology based on surface-enhanced Raman scattering in cancer biomarker detection: A review

Changhong Nie, Ibrahim Shaw, Chuanpin Chen

2023, 13(12): 1429-1451. doi: 10.1016/j.jpha.2023.08.009

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With the continuous discovery and research of predictive cancer-related biomarkers, liquid biopsy shows great potential in cancer diagnosis. Surface-enhanced Raman scattering (SERS) and microfluidic technology have received much attention among the various cancer biomarker detection methods. The former has ultrahigh detection sensitivity and can provide a unique fingerprint. In contrast, the latter has the characteristics of miniaturization and integration, which can realize accurate control of the detection samples and high-throughput detection through design. Both have the potential for point-of-care testing (POCT), and their combination (lab-on-a-chip SERS (LoC-SERS)) shows good compatibility. In this paper, the basic situation of circulating proteins, circulating tumor cells, exosomes, circulating tumor DNA (ctDNA), and microRNA (miRNA) in the diagnosis of various cancers is reviewed, and the detection research of these biomarkers by the LoC-SERS platform in recent years is described in detail. At the same time, the challenges and future development of the platform are discussed at the end of the review. Summarizing the current technology is expected to provide a reference for scholars engaged in related work and interested in this field.

Interactions of naturally occurring compounds with antimicrobials

Izabela Malczak, Anna Gajda

2023, 13(12): 1452-1470. doi: 10.1016/j.jpha.2023.09.014

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Antibiotics are among the most often used medications in human healthcare and agriculture. Overusing these substances can lead to complications such as increasing antibiotic resistance in bacteria or a toxic effect when administering large amounts. To solve these problems, new solutions in antibacterial therapy are needed. The use of natural products in medicine has been known for centuries. Some of them have antibacterial activity, hence the idea to combine their activity with commercial antibiotics to reduce the latter's use. This review presents collected information on natural compounds (terpenes, alkaloids, flavonoids, tannins, sulfoxides, and mycotoxins), of which various drug interactions have been observed. Many of the indicated compounds show synergistic or additive interactions with antibiotics, which suggests their potential for use in antibacterial therapy, reducing the toxicity of the antibiotics used and the risk of further development of bacterial resistance. Unfortunately, there are also compounds which interact antagonistically, potentially hindering the therapy of bacterial infection. Depending on its mechanism of action, each compound can behave differently in combination with different antibiotics and when acting against various bacterial strains.

The role of SLC12A family of cation-chloride cotransporters and drug discovery methodologies

Shiyao Zhang, Nur Farah Meor Azlan, Sunday Solomon Josiah, Jing Zhou, Xiaoxia Zhou, Lingjun Jie, Yanhui Zhang, Cuilian Dai, Dong Liang, Peifeng Li, Zhengqiu Li, Zhen Wang, Yun Wang, Ke Ding, Yan Wang, Jinwei Zhang

2023, 13(12): 1471-1495. doi: 10.1016/j.jpha.2023.09.002

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The solute carrier family 12 (SLC12) of cation-chloride cotransporters (CCCs) comprises potassium chloride cotransporters (KCCs, e.g. KCC1, KCC2, KCC3, and KCC4)-mediated Cl⁻ extrusion, and sodium potassium chloride cotransporters (N[K]CCs, NKCC1, NKCC2, and NCC)-mediated Cl⁻ loading. The CCCs play vital roles in cell volume regulation and ion homeostasis. Gain-of-function or loss-of-function of these ion transporters can cause diseases in many tissues. In recent years, there have been considerable advances in our understanding of CCCs' control mechanisms in cell volume regulations, with many techniques developed in studying the functions and activities of CCCs. Classic approaches to directly measure CCC activity involve assays that measure the transport of potassium substitutes through the CCCs. These techniques include the ammonium pulse technique, radioactive or nonradioactive rubidium ion uptake-assay, and thallium ion-uptake assay. CCCs' activity can also be indirectly observed by measuring γ-aminobutyric acid (GABA) activity with patch-clamp electrophysiology and intracellular chloride concentration with sensitive microelectrodes, radiotracer ³⁶Cl⁻, and fluorescent dyes. Other techniques include directly looking at kinase regulatory sites phosphorylation, flame photometry, ²²Na⁺ uptake assay, structural biology, molecular modeling, and high-throughput drug screening. This review summarizes the role of CCCs in genetic disorders and cell volume regulation, current methods applied in studying CCCs biology, and compounds developed that directly or indirectly target the CCCs for disease treatments.

Integrated mass spectrometry imaging reveals spatial-metabolic alteration in diabetic cardiomyopathy and the intervention effects of ferulic acid

Yanhua Liu, Xin Zhang, Shu Yang, Zhi Zhou, Lu Tian, Wanfang Li, Jinfeng Wei, Zeper Abliz, Zhonghua Wang

2023, 13(12): 1496-1509. doi: 10.1016/j.jpha.2023.08.011

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Diabetic cardiomyopathy (DCM) is a metabolic disease and a leading cause of heart failure among people with diabetes. Mass spectrometry imaging (MSI) is a versatile technique capable of combining the molecular specificity of mass spectrometry (MS) with the spatial information of imaging. In this study, we used MSI to visualize metabolites in the rat heart with high spatial resolution and sensitivity. We optimized the air flow-assisted desorption electrospray ionization (AFADESI)-MSI platform to detect a wide range of metabolites, and then used matrix-assisted laser desorption ionization (MALDI)-MSI for increasing metabolic coverage and improving localization resolution. AFADESI-MSI detected 214 and 149 metabolites in positive and negative analyses of rat heart sections, respectively, while MALDI-MSI detected 61 metabolites in negative analysis. Our study revealed the heterogenous metabolic profile of the heart in a DCM model, with over 105 region-specific changes in the levels of a wide range of metabolite classes, including carbohydrates, amino acids, nucleotides, and their derivatives, fatty acids, glycerol phospholipids, carnitines, and metal ions. The repeated oral administration of ferulic acid during 20 weeks significantly improved most of the metabolic disorders in the DCM model. Our findings provide novel insights into the molecular mechanisms underlying DCM and the potential of ferulic acid as a therapeutic agent for treating this condition.

Pregnenolone 16α-carbonitrile negatively regulates hippocampal cytochrome P450 enzymes and ameliorates phenytoin-induced hippocampal neurotoxicity

Shuai Zhang, Tingting Wang, Ye Feng, Fei Li, Aijuan Qu, Xiuchen Guan, Hui Wang, Dan Xu

2023, 13(12): 1510-1525. doi: 10.1016/j.jpha.2023.07.013

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Abstract:
The central nervous system is susceptible to the modulation of various neurophysiological processes by the cytochrome P450 enzyme (CYP), which plays a crucial role in the metabolism of neurosteroids. The antiepileptic drug phenytoin (PHT) has been observed to induce neuronal side effects in patients, which could be attributed to its induction of CYP expression and testosterone (TES) metabolism in the hippocampus. While pregnane X receptor (PXR) is widely known for its regulatory function of CYPs in the liver, we have discovered that the treatment of mice with pregnenolone 16α-carbonitrile (PCN), a PXR agonist, has differential effects on CYP expression in the liver and hippocampus. Specifically, the PCN treatment resulted in the induction of cytochrome P450, family 3, subfamily a, polypeptide 11 (CYP3A11), and CYP2B10 expression in the liver, while suppressing their expression in the hippocampus. Functionally, the PCN treatment protected mice from PHT-induced hippocampal nerve injury, which was accompanied by the inhibition of TES metabolism in the hippocampus. Mechanistically, we found that the inhibition of hippocampal CYP expression and attenuation of PHT-induced neurotoxicity by PCN were glucocorticoid receptor dependent, rather than PXR independent, as demonstrated by genetic and pharmacological models. In conclusion, our study provides evidence that PCN can negatively regulate hippocampal CYP expression and attenuate PHT-induced hippocampal neurotoxicity independently of PXR. Our findings suggest that glucocorticoids may be a potential therapeutic strategy for managing the neuronal side effects of PHT.

Gut dysbiosis aggravates cognitive deficits, amyloid pathology and lipid metabolism dysregulation in a transgenic mouse model of Alzheimer's disease

Chang Qu, Qing-Qing Xu, Wen Yang, Mei Zhong, Qiuju Yuan, Yan-Fang Xian, Zhi-Xiu Lin

2023, 13(12): 1526-1547. doi: 10.1016/j.jpha.2023.07.014

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Gut dysbiosis, a well-known risk factor to triggers the progression of Alzheimer's disease (AD), is strongly associated with metabolic disturbance. Trimethylamine N-oxide (TMAO), produced in the dietary choline metabolism, has been found to accelerate neurodegeneration in AD pathology. In this study, the cognitive function and gut microbiota of TgCRND8 (Tg) mice of different ages were evaluated by Morris water maze task (MWMT) and 16S rRNA sequencing, respectively. Young pseudo germ-free (PGF) Tg mice that received faecal microbiota transplants from aged Tg mice and wild-type (WT) mice were selected to determine the role of the gut microbiota in the process of neuropathology. Excessive choline treatment for Tg mice was used to investigate the role of abnormal choline metabolism on the cognitive functions. Our results showed that gut dysbiosis, neuroinflammation response, Aβ deposition, tau hyperphosphorylation, TMAO overproduction and cyclin-dependent kinase 5 (CDK5)/transcription 3 (STAT3) activation occurred in Tg mice age-dependently. Disordered microbiota of aged Tg mice accelerated AD pathology in young Tg mice, with the activation of CDK5/STAT3 signaling in the brains. On the contrary, faecal microbiota transplantation from WT mice alleviated the cognitive deficits, attenuated neuroinflammation, Aβ deposition, tau hyperphosphorylation, TMAO overproduction and suppressed CDK5/STAT3 pathway activation in Tg mice. Moreover, excessive choline treatment was also shown to aggravate the cognitive deficits, Aβ deposition, neuroinflammation and CDK5/STAT3 pathway activation. These findings provide a novel insight into the interaction between gut dysbiosis and AD progression, clarifying the important roles of gut microbiota-derived substances such as TMAO in AD neuropathology.

Glutaredoxin-1 alleviates acetaminophen-induced liver injury by decreasing its toxic metabolites

Ying Xu, Yan Xia, Qinhui Liu, Xiandan Jing, Qin Tang, Jinhang Zhang, Qingyi Jia, Zijing Zhang, Jiahui Li, Jiahao Chen, Yimin Xiong, Yanping Li, Jinhan He

2023, 13(12): 1548-1561. doi: 10.1016/j.jpha.2023.08.004

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Excessive N-acetyl-p-benzoquinone imine (NAPQI) formation is a starting event that triggers oxidative stress and subsequent hepatocyte necrosis in acetaminophen (APAP) overdose caused acute liver failure (ALF). S-glutathionylation is a reversible redox post-translational modification and a prospective mechanism of APAP hepatotoxicity. Glutaredoxin-1 (Glrx1), a glutathione-specific thioltransferase, is a primary enzyme to catalyze deglutathionylation. The objective of this study was to explored whether and how Glrx1 is associated with the development of ALF induced by APAP. The Glrx1 knockout mice (Glrx1) and liver-specific overexpression of Glrx1 (AAV8-Glrx1) mice were produced and underwent APAP-induced ALF. Pirfenidone (PFD), a potential inducer of Glrx1, was administrated preceding APAP to assess its protective effects. Our results revealed that the hepatic total protein S-glutathionylation (PSSG) increased and the Glrx1 level reduced in mice after APAP toxicity. Glrx1^−/− mice were more sensitive to APAP overdose, with higher oxidative stress and more toxic metabolites of APAP. This was attributed to Glrx1 deficiency increasing the total hepatic PSSG and the S-glutathionylation of cytochrome p450 3a11 (Cyp3a11), which likely increased the activity of Cyp3a11. Conversely, AAV8-Glrx1 mice were defended against liver damage caused by APAP overdose by inhibiting the S-glutathionylation and activity of Cyp3a11, which reduced the toxic metabolites of APAP and oxidative stress. PFD precede administration upregulated Glrx1 expression and alleviated APAP-induced ALF by decreasing oxidative stress. We have identified the function of Glrx1 mediated PSSG in liver injury caused by APAP overdose. Increasing Glrx1 expression may be investigated for the medical treatment of APAP-caused hepatic injury.

Integrating UHPLC-MS/MS quantitative analysis and exogenous purine supplementation to elucidate the antidepressant mechanism of Chaigui granules by regulating purine metabolism

Jiajun Chen, Tian Li, Dehua Huang, Wenxia Gong, Junsheng Tian, Xiaoxia Gao, Xuemei Qin, Guanhua Du, Yuzhi Zhou

2023, 13(12): 1562-1576. doi: 10.1016/j.jpha.2023.08.008

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Abstract:
Chaigui granules (CG) are a compound composed of six herbal medicines with significant antidepressant effects. However, the antidepressant mechanism of CG remains unclear. In the present study, we attempted to elucidate the antidepressant mechanism of CG by regulating purine metabolism and purinergic signaling. First, the regulatory effect of CG on purine metabolites in the prefrontal cortex (PFC) of chronic unpredictable mild stress (CUMS) rats was analyzed by ultra high-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) targeted quantitative analysis. Meanwhile, purinergic receptors (P2X7 receptor (P2X7R), A₁ receptor (A₁R) and A_2A receptor (A_2AR)) and signaling pathways (nod-like receptor protein 3 (NLRP3) inflammasome pathway and cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) pathway) associated with purine metabolism were analyzed by western blotting and enzyme-linked immunosorbent assay (ELISA). Besides, antidepressant mechanism of CG by modulating purine metabolites to activate purinergic receptors and related signaling pathways was dissected by exogenous supplementation of purine metabolites and antagonism of purinergic receptors in vitro. An in vivo study showed that the decrease in xanthine and the increase in four purine nucleosides were closely related to the antidepressant effects of CG. Additionally, purinergic receptors (P2X7R, A₁R and A_2AR) and related signaling pathways (NLRP3 inflammasome pathway and cAMP-PKA pathway) were also significantly regulated by CG. The results of exogenous supplementation of purine metabolites and antagonism of purinergic receptors showed that excessive accumulation of xanthine led to activation of the P2X7R-NLRP3 inflammasome pathway, and the reduction of adenosine and inosine inhibited the A₁R-cAMP-PKA pathway, which was significantly ameliorated by CG. Overall, CG could promote neuroprotection and ultimately play an antidepressant role by inhibiting the xanthine-P2X7R-NLRP3 inflammasome pathway and activating the adenosine/inosine-A₁R-cAMP-PKA pathway.

Optimization of nucleic acid extraction methods for rapid detection in pandemic situations or diseases with high prevalence

Hesti Lina Wiraswati, Ilma Fauziah Ma'ruf, Savira Ekawardhani, Lia Faridah, Amila Laelalugina, Harry Septanto, Imam Damar Djati, Shabarni Gaffar, Asif Awaludin

2023, 13(12): 1577-1579. doi: 10.1016/j.jpha.2023.08.005

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Corrigendum to “GB7 acetate, a galbulimima alkaloid from Galbulimima belgraveana, possesses anticancer effects in colorectal cancer cells” [J. Pharm. Anal. 12 (2022) 339–349]

Ziyin Li, Lianzhi Mao, Bin Yu, Huahuan Liu, Qiuyu Zhang, Zhongbo Bian, Xudong Zhang, Wenzhen Liao, Suxia Sun

2023, 13(12): 1580-1582. doi: 10.1016/j.jpha.2023.12.014

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2023 Vol. 13, No. 12