Psychoactive Plant Database - Neuroactive Phytochemical Collection

1. Zhongguo Yi Xue Ke Xue Yuan Xue Bao. 2024 Aug 30. doi: 
10.3881/j.issn.1000-503X.16087. Online ahead of print.

[Effect of Sakuranetin on Microglia-Mediated Neuroinflammation After Spinal Cord 
Injury].

[Article in Chinese; Abstract available in Chinese from the publisher]

Xiao LY(1)(2), Chen Y(1)(2), Duan T(2)(3), Sun Y(1)(2), Xu YB(2)(4), Zhao YJ(2), 
Song X(2)(5), Yan XZ(1), Hu JG(2)(6).

Author information:
(1)Department of Rehabilitation,The First Affiliated Hospital of Bengbu Medical 
University,Bengbu,Anhui 233004,China.
(2)Anhui Province Key Laboratory of Basic and Translational Research of 
Inflammation-Related Diseases,The First Affiliated Hospital of Bengbu Medical 
University,Bengbu,Anhui 233004,China.
(3)Department of Emergency Medicine,The First Affiliated Hospital of Bengbu 
Medical University,Bengbu,Anhui 233004,China.
(4)Department of Histology and Embryology,College of Basic Medical 
Sciences,Bengbu Medical University,Bengbu,Anhui 233030,China.
(5)Central Laboratory,The First Affiliated Hospital of Bengbu Medical 
University,Bengbu,Anhui 233004,China.
(6)Clinical Laboratory,The First Affiliated Hospital of Bengbu Medical 
University,Bengbu,Anhui 233004,China.

Objective To investigate the effects of sakuranetin (SK) on motor functions in 
the mouse model of spinal cord injury (SCI) and decipher the mechanism.Methods 
Fifty-four C57BL/6J mice were randomized into sham,SCI,and SK groups.The mice in 
the sham group underwent only laminectomy at T9,while those in the SCI and SK 
groups were subjected to spinal cord contusion injury at T9.Behavioral tests 
were conducted at different time points after surgery to evaluate the motor 
functions of mice in each group.The pathological changes in the tissue were 
observed to assess the extent of SCI in each group.The role and mechanism of SK 
in SCI were predicted by gene ontology (GO) and Kyoto encyclopedia of genes and 
genomes (KEGG) enrichment analyses.Reverse transcription real-time fluorescence 
quantitative PCR,ELISA,and immunofluorescence were employed to evaluate the 
inflammation and activation of microglia in SCI mice.BV2 cells in vitro were 
classified into control (Con),lipopolysaccharide (LPS),and LPS+SK groups.The 
effects of SK intervention on the release of inflammatory cytokines and the 
activation of BV2 cells were evaluated.Furthermore,the 
phosphatidylinositol-3-kinase(PI3K)/protein kinase B (AKT) signaling pathway 
activator insulin-like growth factor-1 (IGF-1) was used to treat the SK-induced 
BV2 cells in vitro (SK+IGF-1 group),and SK was used to treat the IGF-1-induced 
BV2 cells in vitro (IGF-1+SK group).Western blotting was conducted for molecular 
mechanism validation.Results Behavioral tests and histological staining results 
showed that compared with the SCI group,the SK group exhibited improved motor 
abilities and reduced area of damage in the spinal cord tissue (all P<0.001).The 
GO enrichment analysis predicted that SK may be involved in the inflammation 
following SCI.The KEGG enrichment analysis predicted that SK regulated the 
PI3K/Akt pathway to exert the neuroprotective effect.The results from in vitro 
and in vivo experiments showed that SK lowered the levels of tumor necrosis 
factor-α,interleukin-6,and interleukin-1β and inhibited the activation of 
microglia (all P<0.05).The results of Western blotting showed that SK 
down-regulated the phosphorylation levels of PI3K and Akt (all P<0.001) and 
inhibited the IGF-1-induced elevation of PI3K and Akt phosphorylation levels 
(all P<0.001).Conversely,IGF-1 had the opposite effects (P=0.001,P<0.001).The 
results of reverse transcription real-time fluorescence quantitative 
PCR,ELISA,and immunofluorescence showed that the SK+IGF-1 group had higher 
levels of inflammatory cytokines and more activated microglia than the SK 
group(all P<0.05).Conclusion SK may suppress the activation of the PI3K/Akt 
pathway to inhibit the inflammation mediated by SCI-induced activation of 
microglia,ameliorate the pathological damage of the spinal cord tissue,and 
promote the recovery of motor functions in SCI mice.

Publisher: 目的 探讨樱花素对脊髓损伤(SCI)小鼠运动功能的作用及相关机制。方法 
将54只C57BL/6J小鼠随机分为假手术组、SCI组和樱花素组,假手术组小鼠仅行T9椎板切除术,而SCI组及樱花素组小鼠于T9椎节处进行脊髓撞击损伤,在术后的不同时间对各组小鼠进行行为学检测以评估各组小鼠运动能力。采用组织病理学评估各组小鼠SCI程度,通过基因本体和京都基因与基因组百科全书富集分析预测樱花素在SCI中的作用和机制,采用逆转录实时荧光定量PCR、ELISA和免疫荧光检测SCI小鼠体内炎症水平和小胶质细胞活化情况。体外利用脂多糖诱导BV2细胞活化并给予樱花素进行干预,分为对照组、脂多糖组和樱花素组,进一步评估樱花素干预对BV2细胞炎症因子释放和BV2细胞活化情况。采用磷脂酰肌醇-3-激酶/蛋白激酶B(PI3K/Akt)信号通路激活剂[胰岛素样生长因子-1(IGF-1)]体外干预樱花素诱导的BV2细胞(樱花素+IGF-1组),采用樱花素体外干预IGF-1诱导的BV2细胞(IGF-1+樱花素组),Western 
blot进行分子机制验证。结果 
行为学检测及组织学染色结果显示,与SCI组相比,樱花素组小鼠表现出更强的运动能力,且脊髓组织损伤面积明显减少(P均<0.001)。基因本体富集分析显示,樱花素可能参与SCI后的炎症过程,京都基因与基因组百科全书富集分析显示,樱花素可能调控PI3K/Akt通路发挥其神经保护作用。体内外实验结果显示,樱花素显著抑制肿瘤坏死因子-α、白细胞介素-6、白细胞介素-1β等炎症因子水平以及小胶质细胞的活化数量(P均<0.05)。Western 
blot结果显示,樱花素显著降低PI3K及Akt磷酸化水平(P均<0.001)且抑制IGF-1引起的PI3K及Akt磷酸化水平的提高(P均<0.001),而IGF-1的干预作用与之相反(P=0.001,P<0.001)。逆转录实时荧光定量PCR、ELISA及免疫荧光结果显示,樱花素+IGF-1组炎症因子水平和小胶质细胞活化数量较樱花素组均显著增加(P均<0.05)。结论 
樱花素可能通过抑制PI3K/Akt通路的激活抑制SCI后小胶质细胞介导的炎症反应,改善脊髓组织病理损伤并促进SCI小鼠运动功能的恢复。.

DOI: 10.3881/j.issn.1000-503X.16087
PMID: 39212067


2. Sci Total Environ. 2024 Nov 1;949:175015. doi:
10.1016/j.scitotenv.2024.175015.  Epub 2024 Jul 26.

Community metagenomics reveals the processes of cadmium resistance regulated by 
microbial functions in soils with Oryza sativa root exudate input.

Zhu S(1), Zhao W(2), Sun S(2), Yang X(2), Mao H(2), Sheng L(2), Chen Z(3).

Author information:
(1)College of Eco-environment Engineering, Guizhou Minzu University, The Karst 
Environmental Geological Hazard Prevention of Key Laboratory of State Ethnic 
Affairs Commission, Guiyang 550025, China. Electronic address: 
zhusixi2011@163.com.
(2)College of Eco-environment Engineering, Guizhou Minzu University, The Karst 
Environmental Geological Hazard Prevention of Key Laboratory of State Ethnic 
Affairs Commission, Guiyang 550025, China.
(3)Department of Applied Ecology, Faculty of Environmental Sciences, Czech 
University of Life Sciences Prague, Kamýcka 129, Praha-Suchdol 16500, Czech 
Republic.

Plants exert a profound influence on their rhizosphere microbiome through the 
secretion of root exudates, thereby imparting critical effects on their growth 
and overall health. The results unveil that japonica rice showcases a remarkable 
augmentation in its antioxidative stress mechanisms under Cd stress. This 
augmentation is characterized by the sequestration of heavy metal ions within 
the root system and the prodigious secretion of a spectrum of flavonoids, 
including Quercetin, Luteolin, Apigenin, Kaempferide, and Sakuranetin. These 
flavonoids operate as formidable guardians, shielding the plant from oxidative 
damage instigated by Cd-induced stress. Furthermore, the metagenomic analyses 
divulge the transformative potential of flavonoids, as they induce profound 
alterations in the composition and structural dynamics of plant rhizosphere 
microbial communities. These alterations manifest through the recruitment of 
plant growth-promoting bacteria, effectively engineering a conducive milieu for 
japonica rice. In addition, our symbiotic network analysis discerns that 
flavonoid compounds significantly improved the positive correlations among 
dominant species within the rhizosphere of japonica rice. This, in turn, 
bolsters the stability and intricacy of the microenvironmental ecological 
network. KEGG functional analyses reveal a notable upregulation in the 
expression of flavonoid functional genes, specifically cadA, cznA, nccC, and 
czrB, alongside an array of transporters, encompassing RND, ABC, MIT, and 
P-ATPase. These molecular orchestrations distinctly demarcated the rhizosphere 
microbiome of japonica rice, markedly enhancing its tolerance to Cd-induced 
stress. These findings not only shed light on the establishment of Cd-resistant 
bacterial consortia in rice but also herald a promising avenue for the precise 
modulation of plant rhizosphere microbiomes, thereby fortifying the safety and 
efficiency of crop production.

Copyright © 2024 Elsevier B.V. All rights reserved.

DOI: 10.1016/j.scitotenv.2024.175015
PMID: 39069186 [Indexed for MEDLINE]

Conflict of interest statement: Declaration of competing interest The authors 
declare that they have no known competing financial interests or personal 
relationships that could have appeared to influence the work reported in this 
paper.


3. J Ethnopharmacol. 2024 Dec 5;335:118617. doi: 10.1016/j.jep.2024.118617. Epub 
2024 Jul 23.

In vivo anti-gastric ulcer activity of 7-O-methyl aromadendrin and sakuranetin 
via mitigating inflammatory and oxidative stress trails.

Ali DE(1), El-Shiekh RA(2), El Sawy MA(3), Khalifa AA(4), Elblehi SS(5), 
Elsokkary NH(6), Ali MA(4).

Author information:
(1)Department of Pharmacognosy and Natural Products, Faculty of Pharmacy, Pharos 
University in Alexandria, Alexandria, Egypt.
(2)Department of Pharmacognosy, Faculty of Pharmacy, Cairo University, Cairo, 
11562, Egypt. Electronic address: riham.adel@pharma.cu.edu.eg.
(3)Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Pharos 
University in Alexandria, Alexandria, Egypt.
(4)Department of Pharmacology and Therapeutics, Faculty of Pharmacy, Pharos 
University in Alexandria, Alexandria, Egypt.
(5)Department of Pathology, Faculty of Veterinary Medicine, Alexandria 
University, Alexandria, Egypt.
(6)Department of Physiology, Faculty of Medicine, Alexandria University, 
Alexandria, Egypt.

ETHNOPHARMACOLOGICAL RELEVANCE: Eucalyptus genus has been used for a very long 
time in conventional treatment as an anti-ulcer remedy.
AIM OF THE STUDY: The study aimed to explore the gastroprotective potential of 
7-O-methyl aromadendrin (7-OMA), and sakuranetin (SKN) in comparison with 
omeprazole. The study tackled the contribution of their anti-inflammatory, 
antioxidant, and antiapoptotic capabilities to their anti-gastric ulcer effects.
MATERIALS AND METHODS: An ethanol-induced gastric ulcer model in rats was 
adopted and the consequences were confirmed by a molecular docking study.
RESULTS: The oral pretreatment of rats 1 h before ethanol using omeprazole 
(20 mg/kg) or 7-OMA (20 or 40 mg/kg) or SKN (20 or 40 mg/kg) exhibited 
gastroprotective and anti-inflammatory properties to different extents. These 
amendments witnessed as restorations in the stomach histological architecture in 
H and E-stained sections, mucus content in periodic acid-Schiff (PAS) stained 
sections with increased cellular proliferation, as demonstrated by increased 
immunohistochemical staining of PCNA, and increments in stomach COX-1 activity 
and eNOS. The highest dose of SKN showed the best corrections to reach 4.8, 1.8, 
and 2.1 folds increase in PAS, COX-1 and eNOS, respectively as compared to the 
untreated ethanol-induced gastric ulcer group; effects that were comparable to 
that of omeprazole. Moreover, reductions in COX-2 activity, and the protein 
expression of NF-κB, IL-6, TNF-α and NOx, in addition to the gene expression of 
inducible iNOS were also noted. Moreover, the antioxidant and antiapoptotic 
capabilities of omeprazole, 7-OMA, and SKN were perceived. SKN (40 mg/kg) 
succeeded to show the unsurpassed results to reach 293.6%, 237.1%, 274.7%, 
248.2%, and 175.4% in total and reduced GSH, catalase, SOD, and Bcl2, 
respectively, as well as 50.0%, 46.8%, and 52.1 % in oxidized GSSG, TBARS and 
caspase-3, respectively. The gastroprotective potential of the tested compounds 
can be assigned to their anti-inflammatory, antioxidant and antiapoptotic 
properties.7-OMA and SKN were studied using molecular docking into the binding 
sites of the most significant inflammatory targets, including COX-2, TNF-α, 
iNOS, and NF-κB. Pharmacokinetic and physicochemical parameters in silico were 
appropriate.
CONCLUSION: The prophylactic use of 7-OMA and SKN could be considered as an 
add-on to recurrent gastric ulcers and might influence its therapeutic 
approaches.

Copyright © 2024 Elsevier B.V. All rights reserved.

DOI: 10.1016/j.jep.2024.118617
PMID: 39053715 [Indexed for MEDLINE]

Conflict of interest statement: Declaration of Competing interest We wish to 
confirm that there are no known conflicts of interest associated with this 
publication of “In vivo antiulcer activity of 7-O-methyl aromadendrin and 
sakuranetin isolated from Eucalyptus torquata L. via mitigating inflammatory and 
oxidative stress trails.” to be published in Journal of Ethnopharmacology. With 
the submission of this manuscript, I would like to undertake that the 
above-mentioned manuscript has not been published elsewhere, accepted for 
publication elsewhere or under editorial review for publication elsewhere; and 
that my Institute's (Faculty of Pharmacy, Cairo University) representative is 
fully aware of this submission.


4. Genomics. 2024 May;116(3):110850. doi: 10.1016/j.ygeno.2024.110850. Epub 2024 
Apr 27.

Metabolomic and transcriptomic reveal flavonoid biosynthesis and regulation 
mechanism in Phlomoides rotata from different habitats.

Li Z(1), Geng G(2), Xie H(3), Zhou L(3), Wang L(1), Qiao F(4).

Author information:
(1)Key Laboratory of Tibetan Plateau Medicinal Plant and Animal Resources, 
School of Life Sciences, Qinghai Normal University, Xining 810008, China.
(2)Academy of Agricultural and Forestry Sciences, Qinghai University, Xining 
810016, China.
(3)Key Laboratory of Tibetan Plateau Medicinal Plant and Animal Resources, 
School of Life Sciences, Qinghai Normal University, Xining 810008, China; 
Academy of Plateau Science and Sustainability, Qinghai Normal University, Xining 
810008, China.
(4)Key Laboratory of Tibetan Plateau Medicinal Plant and Animal Resources, 
School of Life Sciences, Qinghai Normal University, Xining 810008, China; 
Academy of Plateau Science and Sustainability, Qinghai Normal University, Xining 
810008, China. Electronic address: qiaofnm@163.com.

Phlomoides rotata is a traditional medical plant at 3100-5200 m altitude in the 
Tibet Plateau. In this study, flavonoid metabolites were investigated in P. 
rotata from Henan County (HN), Guoluo County (GL), Yushu County (YS), and 
Chengduo County (CD) habitats in Qinghai. The level of kaempferol 
3-neohesperidoside, sakuranetin, and biochanin A was high in HN. The content of 
limocitrin and isoquercetin was high in YS. The levels of ikarisoside A and 
chrysosplenol D in GL were high. Schaftoside, miquelianin, malvidin chloride, 
and glabrene in CD exhibited high levels. The results showed a significant 
correlation between 59 flavonoids and 29 DEGs. Eleven flavonoids increased with 
altitude. PAL2, UFGT6, COMT1, HCT2, 4CL4, and HCT3 genes were crucial in 
regulating flavonoid biosynthesis. Three enzymes CHS, 4CL, and UFGT, were 
crucial in regulating flavonoid biosynthesis. This study provided biological and 
chemical evidence for the different uses of various regional plants of P. 
rotata.

Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.

DOI: 10.1016/j.ygeno.2024.110850
PMID: 38685286 [Indexed for MEDLINE]

Conflict of interest statement: Declaration of competing interest The authors 
declare that the research was conducted in the absence of any commercial or 
financial relationships that could be construed as a potential conflict of 
interest.


5. Nat Commun. 2024 Apr 23;15(1):3437. doi: 10.1038/s41467-024-47746-y.

Phytoalexin sakuranetin attenuates endocytosis and enhances resistance to rice 
blast.

Jiang L(#)(1), Zhang X(#)(1), Zhao Y(#)(1)(2), Zhu H(1), Fu Q(1), Lu X(1), Huang 
W(1), Yang X(1), Zhou X(1), Wu L(1), Yang A(1), He X(1), Dong M(1), Peng Z(1), 
Yang J(1)(3)(4), Guo L(1)(3)(4), Wen J(5), Huang H(1)(3)(4), Xie Y(1)(3)(4), Zhu 
S(1)(3)(4), Li C(1)(3)(4), He X(6), Zhu Y(1)(3)(4), Friml J(7), Du Y(8)(9)(10).

Author information:
(1)College of Plant Protection, Yunnan Agricultural University, Kunming, 650201, 
China.
(2)Shanxi Agricultural University/Shanxi Academy of Agricultural Sciences. The 
Industrial Crop Institute, Fenyang, 032200, China.
(3)State Key Laboratory for Conservation and Utilization of Bio-Resources in 
Yunnan, Yunnan Agricultural University, Kunming, 650201, China.
(4)Key Laboratory of Agro-Biodiversity and Pest Management of Education Ministry 
of China, Yunnan Agricultural University, Kunming, 650201, China.
(5)Rice Research Institute, Yunnan Agricultural University, Kunming, 650201, 
China.
(6)Key Laboratory for Forest Resources Conservation and Utilization in the 
Southwest Mountains of China, Ministry of Education, Southwest Forestry 
University, Kunming, 650224, China.
(7)Institute of Science and Technology Austria (IST Austria), Klosterneuburg, 
Austria.
(8)College of Plant Protection, Yunnan Agricultural University, Kunming, 650201, 
China. yunlongdu@aliyun.com.
(9)State Key Laboratory for Conservation and Utilization of Bio-Resources in 
Yunnan, Yunnan Agricultural University, Kunming, 650201, China. 
yunlongdu@aliyun.com.
(10)Key Laboratory of Agro-Biodiversity and Pest Management of Education 
Ministry of China, Yunnan Agricultural University, Kunming, 650201, China. 
yunlongdu@aliyun.com.
(#)Contributed equally

Phytoalexin sakuranetin functions in resistance against rice blast. However, the 
mechanisms underlying the effects of sakuranetin remains elusive. Here, we 
report that rice lines expressing resistance (R) genes were found to contain 
high levels of sakuranetin, which correlates with attenuated endocytic 
trafficking of plasma membrane (PM) proteins. Exogenous and endogenous 
sakuranetin attenuates the endocytosis of various PM proteins and the fungal 
effector PWL2. Moreover, accumulation of the avirulence protein AvrCO39, 
resulting from uptake into rice cells by Magnaporthe oryzae, was reduced 
following treatment with sakuranetin. Pharmacological manipulation of 
clathrin-mediated endocytic (CME) suggests that this pathway is targeted by 
sakuranetin. Indeed, attenuation of CME by sakuranetin is sufficient to convey 
resistance against rice blast. Our data reveals a mechanism of rice against M. 
oryzae by increasing sakuranetin levels and repressing the CME of pathogen 
effectors, which is distinct from the action of many R genes that mainly 
function by modulating transcription.

© 2024. The Author(s).

DOI: 10.1038/s41467-024-47746-y
PMCID: PMC11039461
PMID: 38653755 [Indexed for MEDLINE]

Conflict of interest statement: The authors declare no competing interests.