Nauclea Officinalis Research Articles

Discovery of COX-2 and 5-LOX dual targeted inhibitors from Nauclea officinalis by employing a combination of affinity ultrafiltration and HPLC-MS/MS

Discovery of COX-2 and 5-LOX dual targeted inhibitors from Nauclea officinalis by employing a combination of affinity ultrafiltration and HPLC-MS/MS

Strictosamide promotes wound healing through activation of the PI3K/AKT pathway

Nauclea officinalis, as a Chinese medicine in Hainan province, had the effect of treating lower limb ulcers, burn infections. In this paper, we studied the effect of Strictosamide (STR), the main bioactive compound in Nauclea officinals, on wound healing and explored its internal mechanism. Firstly, the wound healing potential of STR was evaluated in a rat model, demonstrating its ability to expedite wound healing, mitigate inflammatory infiltration, and enhance collagen deposition. Additionally, immunofluorescence analysis revealed that STR up-regulated the expression of CD31 and PCNA. Subsequently, target prediction, protein-protein interaction (PPI), gene ontology (GO), and pathway enrichment analyses were used to obtain potential targets, specific biological processes, and molecular mechanisms of STR for the potential treatment of wound healing. Furthermore, molecular docking was conducted to predict the binding affinity between STR and its associated targets. Additionally, in vivo and in vitro experiments confirmed that STR could increase the expression of P-PI3K, P-AKT and P-mTOR by activating the PI3K/AKT signaling pathway. In summary, this study provided a new explanation for the mechanism by which STR promotes wound healing through network pharmacology, suggesting that STR may be a new candidate for treating wound.

Chemical constituents and pharmacological effects of Nauclea officinalis and predictive analysis of its quality markers

Nauclea officinalis is a Chinese medicinal material with a high medicinal value, which contains various chemical constituents such as alkaloids, pentacyclic triterpenoids and their saponins, organic phenolic acids and their glycosides, iridoids, and flavonoids. It has antiviral, antibacterial, antipyretic, analgesic, anti-inflammatory, and immunoregulatory functions. This article systematically reviewed the reported chemical constituents and pharmacological effects of N. officinalis. According to the concept of quality markers, the quality markers of N. officinalis were predicted and analyzed from the aspects of plant kinship, specificity of chemical constituents, traditional drug efficacy, measurability of chemical constituents, plasma components, and different producing areas and harvest times, in order to provide a basis for the quality evaluation of N. officinalis.

Simultaneous and rapid quantification of multi-compounds in Nauclea officinalis based on UPLC-DAD

Nauclea officinalis is a Li-folk medicine in China, with antimalarial, antibacterial, and anti-inflammatory properties. However, the phytochemicals of Nauclea officinalis have not yet been comprehensively researched. In this paper, a reliable and efficient approach based on ultra-performance liquid chromatography (UPLC) with a diode array detector (DAD) was firstly established for simultaneous quantification of alkaloids, flavonoids, and phenolic acids in N. officinalis resources. The samples were extracted using ultrasound with 60 % ethanol for 20 min (1:50 g/mL), and analyzed by the developed UPLC-DAD method. Under the optimized extraction and chromatographic conditions, the proposed approach showed favorable performance in terms of the linearity (R2 > 0.9998), precision (RSD < 3.75 %), repeatability (RSD < 0.86 %), stability (RSD < 2.14 %), and accuracy (with the recovery rates between 95.15 % and 105.49 %) within an extremely short running time (12 min). Moreover, the developed approach was successfully employed in the quantification of ten phytochemicals in different parts (leaves, branches and trunks) of Nauclea officinalis. Based on analytical results, the content of ten phytochemicals in different organs of Nauclea officinalis was significantly different, and the superior contents of these phytochemicals were located in the leaves compared to the branches and trunks. In summary, the current work established an effective method for the assay of multi-compounds, which could supply a basis of the quality control and comprehensive utilization for Nauclea officinalis.

Exploring binding potential of two new indole alkaloids from Nauclea officinalis against third and fourth generation EGFR: druglikeness, in silico ADMET, docking, DFT, molecular dynamics simulation, and MMGBSA study

This study investigates the anti-cancer potential of recently discovered indole alkaloids from Nauclea Officinalis against third and fourth-generation EGFR mutations using computational tools. Through ADMET profiling, druglikeness prediction, docking, and simulations, we assessed their pharmacokinetics, binding interactions, and stability. Promising druglikeness and binding affinity were observed, particularly for (±)-19-O-butylangustoline, which demonstrated stronger binding against both EGFR mutants. MD simulations confirmed stable interactions, with (±)-19-O-butylangustoline exhibiting the highest stability. These findings highlight these indole alkaloids as potential anti-cancer agents, with (±)-19-O-butylangustoline warranting further optimisation for therapeutic development. This study informs their potential through insights into molecular properties and binding energetics.

Strictosamide ameliorates LPS-induced acute lung injury by targeting ERK2 and mediating NF-κB signaling pathway

Ethnopharmacological relevanceAcute lung injury (ALI) ranks among the deadliest pulmonary diseases, significantly impacting mortality and morbidity. Presently, the primary treatment for ALI involves supportive therapy; however, its efficacy remains unsatisfactory. Strictosamide (STR), an indole alkaloid found in the Chinese herbal medicine Nauclea officinalis (Pierre ex Pit.) Merr. & Chun (Wutan), has been found to exhibit numerous pharmacological properties, particularly anti-inflammatory effects. Aim of the studyThis study aimes to systematically identify and validate the specific binding proteins targeted by STR and elucidate its anti-inflammatory mechanism in lipopolysaccharide (LPS)-induced ALI. Materials and methodsBiotin chemical modification, protein microarray analysis and network pharmacology were conducted to screen for potential STR-binding proteins. The binding affinity was assessed through surface plasmon resonance (SPR), cellular thermal shift assay (CETSA) and molecular docking, and the anti-inflammatory mechanism of STR in ALI treatment was assessed through in vivo and in vitro experiments. ResultsBiotin chemical modification, protein microarray and network pharmacology identified extracellular-signal-regulated kinase 2 (ERK2) as the most important binding proteins among 276 candidate STR-interacting proteins and nuclear factor-kappaB (NF-κB) pathway was one of the main inflammatory signal transduction pathways. Using SPR, CETSA, and molecular docking, we confirmed STR's affinity for ERK2. In vitro and in vivo experiments demonstrated that STR mitigated inflammation by targeting ERK2 to modulate the NF-κB signaling pathway in LPS-induced ALI. ConclusionsOur findings indicate that STR can inhibit the NF-κB signaling pathway to attenuate LPS-induced inflammation by targeting ERK2 and decreasing phosphorylation of ERK2, which could be a novel strategy for treating ALI.

Optimization of ethanol precipitation process of Nauclea officinalis extract based on concept of quality by design(QbD)

The ethanol precipitation process of Nauclea officinalis extract was optimized based on the concept of quality by design(QbD). Single factor tests were carried out to determine the levels of test factors. The ethanol volume fraction, pre-ethanol precipitation drug concentration, and ethanol precipitation time were taken as critical process parameters(CPPs). With the comprehensive scores of strictosamide transfer rate and solid removal rate as the critical quality attributes(CQAs), Box-Behnken design was employed to establish the mathematical models and space design between CPPs and CQAs, and the obtained optimal operating space was validated. The optimal operating space included ethanol volume fraction of 65%-70%, pre-ethanol precipitation drug concentration of 22-27 mg·mL~(-1), and ethanol precipitation time of 12 h. Based on the concept of QbD, this study adopted the design space to optimize the ethanol precipitation process of N. officinalis extract, which provided a reliable theoretical basis for the quality control in the production process of N. officinalis preparations. Moroever, this study provided a reference value for guiding the research and industrial production of traditional Chinese medicines.

Two new indole alkaloids from Nauclea officinalis and their evaluation for cytotoxic activities

Two new indole alkaloids, naucleamide H (1) and (±)-19-O-butylangustoline (8), along with seven known alkaloids, 3,14-dihydroangustine (2), (-)-naucleofficine D (3a), (+)-naucleofficine D (3b), nauclefine (4), angustidine (5),19-O-ethylangustoline (6) and angustine (7) were isolated from the water extract of Nauclea officinalis. The structures of these compounds were established by spectroscopic analysis. Among them, the cytotoxicity of 1, 2, 6 and 8 were evaluated against six human cancer cell lines (HepG-2, SKOV3, HeLa, SGC 7901, MCF-7 and KB) in vitro for the first time with 5-fluorouracil as a positive control drug. The new compound 1 had a strong inhibitory effect on the proliferation of HepG-2 with an IC50 value of 19.59 μg/mL. The new compound 8 had a strong inhibitory effect on HepG-2, SKOV3, HeLa, MCF-7 and KB, IC50 value was 5.530, 23.11, 31.30, 32.42 and 37.26 μg/mL, respectively.

Neuroprotective Activities of New Monoterpenoid Indole Alkaloid from Nauclea officinalis

Phytochemical investigation on the bark of Nauclea officinalis led to the isolation of a new monoterpenoid indole alkaloid, nauclediol. The structure of the compound was identified through extensive spectroscopic analysis. Nauclediol displayed cholinesterase-inhibitory activities towards AChE and BChE with IC50 values of 15.429 and 8.756 µM, respectively. Statistical analysis revealed that the mode of inhibition of nauclediol was non-competitive inhibitor for both AChE and BChE. Molecular docking revealed that nauclediol interacts with the choline-binding site and the catalytic triad of TcAChE and hBChE. This study also demonstrated the neuroprotective potential of nauclediol against amyloid beta-induced cytotoxicity and LPS-induced neuroinflammation activity in a dose-dependent manner.

Measurement of Pharmacokinetics and Tissue Distribution of Four Compounds from Nauclea officinalis in Rat Plasma and Tissues through HPLC-MS/MS.

A rapid, sensitive, selective, and accurate HPLC-MS/MS method was developed and validated for the simultaneous determination of chlorogenic acid, naucleactonin C, khaephuoside A 3,4-dimethoxyphenyl-1-O-β-apiofuroseyl(1 ⟶ 2)-β-D-glucopyranoside in rat plasma and tissues after oral administration of Nauclea officinalis extracts. Chloramphenicol was used as an internal standard (IS). The plasma and tissue samples were extracted by protein precipitation with methanol-ethyl acetate (1 : 1, v/v) including 0.1% (v/v) formic acid. The chromatographic separation was achieved by using an C18 column with gradient elution using mobile phase, which consisted of 0.1% formic acid water (A) and acetonitrile (B) and the flow rate of 0.8 mL/min. Mass spectrometric detection was performed in multiple reaction monitoring (MRM) mode utilizing electrospray ionization (ESI) in negative mode. The developed method exhibited good linearity (determination coefficients, R 2 ≥ 0.9849), and the lower limits of quantification were 2, 5, 5, and 25 ng/mL for chlorogenic acid, naucleactonin C, khaephuoside A, and 3,4-dimethoxyphenyl-1-O-β-apiofuroseyl(1 ⟶ 2)-β-D-glucopyranoside. The intraday and interday precisions (relative standard deviation, RSD) were less than 12.65%, while the accuracy was ranged from 86.31 to 114.17%. The recovery rate were 51.85-97.06%, 75.99-106.68%, 77.46-105.35%, and 68.36-103.75% for chlorogenic acid, naucleactonin C, khaephuoside A, and 3,4-dimethoxyphenyl-1-O-β-apiofuroseyl(1 ⟶ 2)-β-D-glucopyranoside the matrix effects were 50.17-116.62%, 86.75-115.99%, 45.79-87.44%, and 51.60-92.34% for chlorogenic acid, naucleactonin C, khaephuoside A, and 3,4-dimethoxyphenyl-1-O-β-apiofuroseyl(1 ⟶ 2)-β-D-glucopyranoside in different matrix. The developed method was successfully applied to a pharmacokinetic study and tissue distribution of four compounds in rats after oral administration of Nauclea officinalis extracts.

Integrated metabolomics, network pharmacology and biological verification to reveal the mechanisms of Nauclea officinalis treatment of LPS-induced acute lung injury

BackgroundAcute lung injury (ALI) is a severe inflammatory disease, underscoring the urgent need for novel treatments. Nauclea officinalis Pierre ex Pitard (Danmu in Chinese, DM) is effective in treating inflammatory respiratory diseases. However, there is still no evidence of its protective effect against ALI.MethodsMetabolomics was applied to identify the potential biomarkers and pathways in ALI treated with DM. Further, network pharmacology was introduced to predict the key targets of DM against ALI. Then, the potential pathways and key targets were further verified by immunohistochemistry and western blot assays.ResultsDM significantly improved lung histopathological characteristics and inflammatory response in LPS-induced ALI. Metabolomics analysis showed that 16 and 19 differential metabolites were identified in plasma and lung tissue, respectively, and most of these metabolites tended to recover after DM treatment. Network pharmacology analysis revealed that the PI3K/Akt pathway may be the main signaling pathway of DM against ALI. The integrated analysis of metabolomics and network pharmacology identified 10 key genes. These genes are closely related to inflammatory response and cell apoptosis of lipopolysaccharide (LPS)-induced ALI in mice. Furthermore, immunohistochemistry and western blot verified that DM could regulate inflammatory response and cell apoptosis by affecting the PI3K/Akt pathway, and expression changes in Bax and Bcl-2 were also triggered.ConclusionThis study first integrated metabolomics, network pharmacology and biological verification to investigate the potential mechanism of DM in treating ALI, which is related to the regulation of inflammatory response and cell apoptosis. And the integrated analysis can provide new strategies and ideas for the study of traditional Chinese medicines in the treatment of ALI.Graphical

Two new neolignans and an indole alkaloid from the stems of Nauclea officinalis and their biological activities

A pair of new diastereoisomers neolignans (1–2) and a new alkaloid (7) were isolated from the stems of Nauclea officinalis: naucleaoxyneolignoside A (1), naucleaoxyneolignoside B (2), (2S,3S)-javaniside (7), together with nine known compounds, 2S-3,3-di-(4-hydroxy-3-methoxyphenyl)-propane-1,2-diol (3), threo-1,2-bis-(4-hydroxy-3-methoxyphenyl)-propane-1,3-diol (4), nauclefine (5), angustidine (6), naucleoxoside A (8), naucleoxoside B (9), angustoline (10), (3S,19S)-3,14-dihydroangustoline (11), and (3S,19R)-3,14-dihydroangustoline (12).The structures of 1, 2 and 7 were elucidated by extensive spectroscopic methods and the known compounds were identified by comparison of their data with those reported in the literature. The absolution configurations of 1, 2, 7,11 and 12 were confirmed by the quantum chemical CD calculation method. Compounds 1–9 showed weak to moderate inhibitory activity on nitric oxide (NO) production induced by lipopolysaccharide in mouse macrophage RAW 264.7 cells in vitro with IC50 values comparable to that of dexamethasone. In addition, compounds 1–9 were evaluated for the antibacterial and cytotoxic effects, and the results revealed that these compounds showed no anti-bacterial activity, and compounds 3–6 showed modest cytotoxic activity.

Two New Neolignans and an Indole Alkaloid from the Stems of Nauclea Officinalis and Their Biological Activities

Two New Neolignans and an Indole Alkaloid from the Stems of Nauclea Officinalis and Their Biological Activities

Comparative analysis of bioactive constituents and pharmacological activities from different parts of Nauclea officinalis.

The stems of Nauclea officinalis have been utilized as a crude drug in China, so other parts of the plant are abandoned, resulting in a waste of traditional Chinese medicine resources. To determine the distribution and content of the alkaloids, phenolic acids and iridoid in different organs (stem, branch, leaf and bark) of this plant, a reliable method has been established using LC-MS/MS. Nine constituents, namely strictosamide, vincosamide, chlorogenic acid, sweroside, naucleamide B, protocatechuic acid, pumiloside, vanillic acid and cryptochlorogenic acid, were simultaneously determined in 6 min. Meanwhile, the antipyretic, anti-inflammatory and analgesic activities were evaluated for comparative analysis of the pharmacological activity of different parts of N. officinalis. The results showed that the content of active components in other organs of N. officinalis was higher than that in stems, and the pharmacological effects of branches and leaves were also better. The established approach could be helpful for the quality control of N. officinalis, and also provide necessary information for the rational utilization of resources.

Land cover and Proboscis monkey habitats in Berau Delta, East Kalimantan

The proboscis monkey is an endangered primate endemic to Borneo. Most of their habitats are outside conservation areas and are under threat from conversion to other land uses, such as those found in the Berau Delta. Habitat loss and destruction significantly affect the quality and viability of the proboscis monkey population. This study aims to determine land cover and proboscis monkey habitat types in Berau Delta. Land cover was obtained from the interpretation of the Lansat 8 OLI 2019 satellite image. Vegetation data were collected using a line plot transect method and continued with cluster analysis. The results showed that mangrove forest has the largest coverage (35.92%), followed by secondary forest (17.10%) and riparian forest (12.96%). At least 74 species of woody plants belonging to 61 genera and 37 families in a 2.4 ha observation plot. The range of species diversity index was from 0.80 to 2.88, and; evenness index values range from 0.58 to 0.82. The habitat was categorized into two main clusters: mangrove cluster (Buasin Cape, Guntung Estuary) and riverine cluster (Lati River, Saodang Kecil Island, Batu-Batu, Bebanir Lama). The mangrove forest habitat consists of Rhizophora mucronata, R. apiculata, Bruguiera sp, Sonneratia alba, and Avicennia alba. The riparian habitats are dominated by Sonneratia caseolaris, Vitex pinnata, Cerbera manghas, Brownlowia argentata, Heritiera littoralis, Syzygium lineatum, Nauclea officinalis, Xylocarpus granatum, Syzygium sp.1, and A. alba. The average of total and lower branches height of trees in the Lati River and Basin Cape were higher than in other habitats, forming a continuous canopy.

The rapid profiling and simultaneous determination of 12 major alkaloids in Nauclea officinalis by UPLC-Q-TOF-MS and HPLC-ESI-MS/MS.

For the first time, we determined the phytochemical profile of alkaloids from N. officinalis using ultraperformance liquid chromatography-quadrupole-time-of-flight-tandem mass spectrometry (UPLC-Q-TOF-MS/MS). A rapid, specific, and sensitive high-performance liquid chromatography-tandem mass spectrometry method was subsequently developed and fully validated for the simultaneous determination of 12 major alkaloid constituents in N. officinalis: pumiloside; naucleoxoside A; naucleoxoside B; nauclefine; angustidine; angustoline; (3S,19S)-3,14-dihydroangustoline ([α]20D: (-)191°); (3S,19R)-3,14-dihydroangustoline ([α]20D: (-)294.7°); strictosamide; angustine; vincosamide; and 3,14-dihydroangustine. The analytes were detected with an electrospray ionization (ESI) source and multiple reaction monitoring (MRM) using positive scanning mode. Three pairs of epimers (naucleoxoside A and naucleoxoside B; (3S,19S)-3,14-dihydroangustoline ([α]20D: (-)191°) and (3S,19R)-3,14-dihydroangustoline ([α]20D: (-)294.7°); and strictosamide and vincosamide) were successfully separated using an ACQUITY UPLC® BEH C18 column (2.1 mm × 100 mm, 1.7 μm) at 30 °C, with a gradient mobile phase consisting of 0.1% formic acid aqueous solution (A) and acetonitrile (B), a flow rate of 0.2 mL min-1, and a total run time of 30 min. All calibration curves exhibited excellent linear regression (r > 0.999) within the test range. The precision, repeatability, and stability of the method toward the 12 alkaloid compounds were less than 2.0% in terms of the relative standard deviation (RSD) values. The mean recoveries for all compounds were between 98.7% and 101.1%, with RSD values ranging from 0.55% to 1.7% for N. officinalis samples.

Simultaneous Quantification of Five Compounds from Nauclea officinalis Leaves by High Performance Liquid Chromatography

A simple, rapid and validated method was developed for the simultaneous determination of five characteristic components, including three alkaloids (pumiloside, 10 - hydroxy strictosamide, and strictosamide), and two flavonoids (rutin and kaempferol-3-O-rutinoside), in the Nauclea officinalis leaves. The chromatographic separation was achieved with a lichrospher C-18 analytical column by gradient elution with (A) 0.1% aqueous phosphoric acid and (B) acetonitrile as mobile phase, with a flow rate of 1.0 mL/min. The column temperature was set at 30℃. Detection was carried out on a photodiode array detector at 226 nm. The method was validated for system suitability, precision, accuracy and lincarity. The average recovery of the method was 98.00 - 100.44% and Iinearity (r) was＞0.9993. Furthermore, the method was successfully applied to the simultaneous determination of five analytes in 10 samples of N. officinalis leaves from different harvesting time of the herb. The results suggested that the method could be efficiently employed to evaluate the quality of N. officinalis leaves from various sources, which would benefit its quality control.

Chromatographic fingerprints analysis and determination of seven components in Danmu preparations by HPLC\u2013DAD/QTOF-MS

BackgroundDanmu preparations (Danmu Capsule and Danmu Syrup), which are made from Nauclea officinalis stem extracts, have good clinical efficacy in acute tonsillitis, acute pharyngitis and upper respiratory tract infection. However, there is currently no reliable and systematic method to control the quality of these two Danmu preparations.MethodsUsing high-performance liquid chromatography (HPLC) coupled with diode array detection (DAD), the fingerprints of the Danmu preparations were established at 250 nm to comprehensively investigate the stability of preparation process. The chemical constituents in the Danmu preparations were separated and identified by HPLC coupled with quadrupole-time-of-flight high-definition mass spectrometry (HPLC–Q-TOF-MS). And seven major components were simultaneously determined at dual wavelengths (250 nm, 326 nm).ResultsThe results of HPLC fingerprint similarity evaluation showed that the similarity values of 25 batches of Danmu preparations were more than 0.993. Twenty-three compounds, including 10 alkaloids, 6 phenolic acids, 2 iridoids, and 5 unknown compounds, were identified or tentatively characterized according to the retention times and MS/MS fragment patterns of compounds. The developed assay method of seven components was validated with acceptable linearity, precision, repeatability, stability and recovery. The contents of strictosamide belonging to alkaloids as the most abundant constituent in Danmu Capsule and Danmu Syrup were 43,681.20–99,652.49 μg/g and 1567.83–2427.25 μg/mL respectively. The contents of protocatechuic acid which were the highest in measured phenolic acids were 2633.01–7739.78 μg/g in Danmu Capsule and 192.05–448.71 μg/mL in Danmu Syrup, respectively. As an iridoid, the contents of sweroside in Danmu Capsule and Danmu Syrup were 1573.82–2789.81 μg/g and 70.32–182.81 μg/mL, respectively.ConclusionThe established qualitative analysis method of fingerprint can be used to attain standardization, uniformity and stability of the preparation process. Meanwhile, the quantitative analysis in this study can be used as an accurate assay method for preparations.

A new indole alkaloid with HUVEC proliferation activities from Nauclea officinalis

A new indole alkaloid, namely naucleofficine H (1), was obtained from the aqueous extract of Nauclea officinalis, together with four known alkaloids, vincosamide (2), strictosamide (3), angustoline (4) and pumiloside (5). Their structures were characterized by analyzing their physicochemical data including NMR, and HRMS. In addition, five compounds were tested for their proliferation activities. The expression of vascular endothelial growth factor (VEGF), extra-cellular signal-regulated protein kinase 1 and 2 (ERK) and phosphorylation of ERK 1/2 (p-ERK) were also detected in HUVEC treated withbioactive compounds using western blotting. The result showed that these compounds could promote HUVEC cell proliferation. Compounds 3 and 5 could up-regulate VEGF and p-ERK in HUVEC.

In vitro anti-inflammatory activities of naucleoffieine H as a natural alkaloid from Nauclea officinalis Pierrc ex Pitard, through inhibition of the iNOS pathway in LPS-activated RAW 264.7 macrophages

Naucleoffieine H, a natural indole alkaloid, was isolated and identified from Nauclea officinalis Pierrc ex Pitard which is a traditional Chinese medicine used for the treatment of various diseases, such as cold, fever, bronchitis, pneumonia, acute tonsillitis, etc. In the present study, the effect of naucleoffieine H on the anti-inflammatory activities was investigated in LPS-induced RAW 264.7 macrophages. The results showed that naucleoffieine H significantly inhibited the release of nitric oxide (the level of nitrite as a stable biomarker of NO production) and tumor necrosis factor-α (TNF-α). Interesting, naucleoffieine H down-regulated the overexpression of inflammatory protein induced nitric oxide synthase (iNOS), but no effect on the expression cyclooxygenase-2 (COX-2) protein. In addition, this bioactive alkaloid suppressed enzymatic activity of iNOS activated by LPS. The above results indicated that naucleoffieine H suppress NO and TNF-α overproduction via block the iNOS pathway in LPS-induced RAW 264.7 macrophages.