Psychoactive Plant Database - Neuroactive Phytochemical Collection

1. Pak J Pharm Sci. 2024 Jan;37(1):65-70.

Leonuride protects diabetic nephropathy by activating SREBPs pathway.

Ma L(1), Zhang X(1), Li Y(1), Bai D(1).

Author information:
(1)The Affiliated Taian City Central Hospital of Qingdao University, Taian, 
China.

Diabetic nephropathy (DN), a micro vascular complication of diabetes, is the 
main cause of end-stage renal disease, with a morbidity over 40% of diabetes. 
High glucose and lipid metabolism dysfunction are the leading cause of the 
development of DN. Previous study demonstrated that increased expression or 
activation of SREBPs in models of DN. Leonuride (LE), as an active constituent 
of Leonurus japonicus Houttuyn, has multiple biological activities, including 
antioxidant and anti-inflammatory effects. Previous studies showed that 
increasing the degradation of mature SREBPs is a robust way of lowering lipids 
and improve lipid metabolism dysfunction. However, effective regulation method 
of SREBPs degradation are still lacking. Herein, this study indicated that LE 
can effectively improve glucose and lipid metabolism disorders. In addition, the 
kidney function was also improved by inhibition of SREBPs activities in 
streptozocin (STZ)-induced type II diabetic mice. To our knowledge, this is the 
first time to describe the detailed mechanism of LE on the inhibition of 
precursor SREBPs, which would present a new direction for diabetic nephropathy 
treatment.

PMID: 38741401 [Indexed for MEDLINE]


2. Phytomedicine. 2022 Oct;105:154345. doi: 10.1016/j.phymed.2022.154345. Epub
2022  Jul 22.

A novel iridoid glycoside leonuride (ajugol) attenuates airway inflammation and 
remodeling through inhibiting type-2 high cytokine/chemokine activity in 
OVA-induced asthmatic mice.

Yi L(1), Zhou Y(2), Song J(2), Tang W(2), Yu H(2), Huang X(2), Shi H(2), Chen 
M(2), Sun J(2), Wei Y(3), Dong J(4).

Author information:
(1)Department of Integrative Medicine, Huashan Hospital, Fudan University, 
Shanghai, China.
(2)Department of Integrative Medicine, Huashan Hospital, Fudan University, 
Shanghai, China; Institutes of Integrative Medicine, Fudan University, Shanghai, 
China.
(3)Department of Integrative Medicine, Huashan Hospital, Fudan University, 
Shanghai, China; Institutes of Integrative Medicine, Fudan University, Shanghai, 
China. Electronic address: weiying_acup@126.com.
(4)Department of Integrative Medicine, Huashan Hospital, Fudan University, 
Shanghai, China; Institutes of Integrative Medicine, Fudan University, Shanghai, 
China. Electronic address: jcdong2004@126.com.

BACKGROUND: Asthma is a chronic airway disorder with a hallmark feature of 
airflow obstruction that associated with the remodeling and inflammation in the 
airway wall. Effective therapy for controlling both remodeling and inflammation 
is still urgently needed. Leonuride is the main pharmacological component 
identified from Bu-Shen-Yi-Qi-Tang (BSYQT) which has been traditionally used in 
treatment of lung diseases. However, no pharmacological effects of leonuride in 
asthma were reported.
PURPOSE: Here we aimed to investigated whether leonuride provided a therapeutic 
efficacy in reversing asthma airway remodeling and inflammation and uncover the 
underlying mechanisms.
STUDY DESIGN AND METHODS: Mouse models of chronic asthma were developed with 
ovalbumin (OVA) exposure for 8 weeks. Respiratory mechanics, lung histopathology 
and asthma-related cytokines were examined. Lung tissues were analyzed using RNA 
sequencing to reveal the transcriptional profiling changes.
RESULTS: After oral administration with leonuride (15 mg/kg or 30 mg/kg), mice 
exhibited a lower airway hyperresponsiveness in comparison to asthmatic mice. 
Leonuride suppressed airway inflammation evidenced by the significant reductions 
in accumulation of inflammatory cells around bronchi and vessels, leukocyte 
population counts and the abundance of type 2 inflammatory mediators (OVA 
specific IgE, IL-4, IL-5 and IL-13) in bronchoalveolar lavage fluid (BALF). On 
the other hand, leonuride slowed down the process of active remodeling as 
demonstrated by weaker goblet cell metaplasia and subepithelial fibrosis in lung 
histopathology and lower transforming growth factor (TGF)-β1 levels in serum and 
BALF in comparison to mice treated with OVA only. Furthermore, we uncovered 
transcriptional profiling alternations in lung tissue of mice after OVA exposure 
and leonuride treatment. Gene sets belonging to type-2 cytokine/chemokine 
activity stood out in leonuride target transcripts. Those upregulated (Bmp10, 
Ccl12, Ccl22, Ccl8, Ccl9, Cxcl15, Il13, Il33, Tnfrsf9, Il31ra, Il5ra, Il13ra2 
and Ccl24) or downregulated (Acvr1c and Il18) genes in asthmatic mice, were all 
reversely regulated by leonuride treatment.
CONCLUSIONS: Our results revealed the therapeutic efficacy of leonuride in 
experimental chronic asthma for the first time, and implied that its 
anti-inflammatory and antifibrotic properties might be mediated by regulation of 
type-2 high cytokine/chemokines responses.

Copyright © 2022. Published by Elsevier GmbH.

DOI: 10.1016/j.phymed.2022.154345
PMID: 35905568 [Indexed for MEDLINE]


3. Chin J Nat Med. 2021 Jul;19(7):551-560. doi: 10.1016/S1875-5364(21)60056-0.

A combined quality evaluation method that integrates chemical constituents, 
appearance traits and origins of raw Rehmanniae Radix pieces.

Gu M(1), Yuan YP(2), Qin ZN(2), Xu Y(2), Shi NN(3), Wang YP(3), Zhai HQ(4), Qian 
ZZ(5).

Author information:
(1)Standardization Research Center of Traditional Chinese Medicine Dispensing, 
Beijing University of Chinese Medicine, Beijing 102488, China. Electronic 
address: 2781352102@qq.com.
(2)Standardization Research Center of Traditional Chinese Medicine Dispensing, 
Beijing University of Chinese Medicine, Beijing 102488, China.
(3)Institute of Basic Research in Clinical Medicine, China Academy of Chinese 
Medical Sciences, Beijing 100700, China.
(4)Standardization Research Center of Traditional Chinese Medicine Dispensing, 
Beijing University of Chinese Medicine, Beijing 102488, China. Electronic 
address: jz711@qq.com.
(5)National Pharmacopoeia Commission, Beijing 100061, China. Electronic address: 
n201801@126.com.

The quality control of Chinese herbal medicine is a current challenge for the 
internationalization of traditional Chinese medicine. Traditional quality 
evaluation methods lack quantitative analysis, while modern quality evaluation 
methods ignore the origins and appearance traits. Therefore, an integrated 
quality evaluation method is urgent in need. Raw Rehmanniae Radix (RRR) is 
commonly used in Chinese herbal medicine. At present, much attention has been 
drwan towards its quality control, which however is limited by the existing 
quality evaluation methods. The present study was designed to establish a 
comprehensive and practical method for the quality evaluation and control of RRR 
pieces based on its chemical constituents, appearance traits and origins. 
Thirty-three batches of RRR pieces were collected from six provinces, while 
high-performance liquid chromatography (HPLC) was applied to determine the 
following five constituents, including catalpol, rehmannioside A, rehmannioside 
D, leonuride and verbascoside in RRR pieces. Their appearance traits were 
quantitatively observed. Furthermore, correlation analysis, principal components 
analysis (PCA), cluster analysis and t-test were performed to evaluate the 
qualities of RRR pieces. These batches of RRR pieces were divided into three 
categories: samples from Henan province, samples from Shandong and Shanxi 
provinces, and those from other provinces. Furthermore, the chemical 
constituents and appearance traits of RRR pieces were significantly different 
from diverse origins. The combined method of chemical contituents, appearance 
traits and origins can distinguish RRR pieces with different qualities, which 
provides basic reference for the quality control of Chinese herbal medicine.

Copyright © 2021 China Pharmaceutical University. Published by Elsevier B.V. All 
rights reserved.

DOI: 10.1016/S1875-5364(21)60056-0
PMID: 34247780 [Indexed for MEDLINE]


4. J Ethnopharmacol. 2021 Aug 10;276:114177. doi: 10.1016/j.jep.2021.114177. Epub
 2021 May 1.

Reverse tracing anti-thrombotic active ingredients from dried Rehmannia Radix 
based on multidimensional spectrum-effect relationship analysis of steaming and 
drying for nine cycles.

Gong PY(1), Guo YJ(2), Tian YS(3), Gu LF(4), Qi J(5), Yu BY(6).

Author information:
(1)Research Center for Traceability and Standardization of TCMs, School of 
Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 211198, 
China; College of Pharmacy, Southwest Minzu University, Chengdu, 610041, China. 
Electronic address: gongpuyang1990@163.com.
(2)Research Center for Traceability and Standardization of TCMs, School of 
Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 211198, 
China. Electronic address: guoyoga@126.com.
(3)Research Center for Traceability and Standardization of TCMs, School of 
Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 211198, 
China. Electronic address: yushantian126163@126.com.
(4)Research Center for Traceability and Standardization of TCMs, School of 
Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 211198, 
China. Electronic address: liphiegu@gmail.com.
(5)Research Center for Traceability and Standardization of TCMs, School of 
Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 211198, 
China; State Key Laboratory of Natural Medicines, School of Traditional Chinese 
Pharmacy, China Pharmaceutical University, Nanjing, 210009, China. Electronic 
address: qijin2006@163.com.
(6)Research Center for Traceability and Standardization of TCMs, School of 
Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, 211198, 
China; State Key Laboratory of Natural Medicines, School of Traditional Chinese 
Pharmacy, China Pharmaceutical University, Nanjing, 210009, China. Electronic 
address: boyangyu59@163.com.

ETHNOPHARMACOLOGICAL RELEVANCE: In traditional Chinese medicine (TCM) and modern 
pharmacodynamics, dried Rehmannia Radix (DRR) possesses prominent 
anti-thrombotic activity that decreases after processing by nine steaming and 
drying cycles to develop processed Rehmannia Radix (PRR). Due to the complexity 
of the DRR components, the chemical mechanism leading to efficacy changes of DRR 
caused by processing is still unclear.
AIM OF STUDY: This study aimed to trace the anti-thrombotic active compounds of 
DRR and different degrees of processed RR (PRR) and to evaluate the synergistic 
effects among different active components.
MATERIALS AND METHODS: The anti-thrombotic active chemical fraction of DRR 
extracts was evaluated. Targeted fractions of the processed products of RR were 
prepared at different processing stages. The changes in monosaccharides, 
oligosaccharides and secondary metabolites during processing were characterized 
by multidimensional high-performance liquid chromatography (HPLC). The 
anti-thrombotic effects of targeted fractions of different RR samples were 
evaluated by analyzing the length of tail thrombus (LT) and serum biochemical 
indicators in carrageenan-induced tail-thrombus mice. The spectrum-effect 
relationships were investigated by partial least squares regression (PLSR) 
analysis and gray correlation analysis (GRA). Finally, the active compounds were 
screened by spectrum-effect relationship analysis and validated in vivo, and 
their synergistic effects were determined by Webb's fraction multiplication 
method.
RESULTS: Six ingredients highly associated with anti-thrombotic activities were 
screened out by the spectrum-effect relationship analysis, of which 
oligosaccharides (stachyose, sucrose and raffinose) and iridoid glycosides 
(catalpol, leonuride and melitoside) possessed a synergistic effect on tumor 
necrosis factors (TNF-α), interleukin 1β (IL-1β) and plasminogen activator 
inhibitor 1 (PAI-1)/tissue-type plasminogen activator (t-PA) ratio in vivo with 
synergistic coefficient (SC) > 1.
CONCLUSION: The main material basis of the anti-thrombotic activities of DRR is 
oligosaccharide components of stachyose, raffinose and sucrose, iridoid 
glycosides components of catalpol, leonuride and melittoside. The two kinds of 
components exert synergistic anti-thrombotic effects by inhibiting the 
expression of inflammatory factors and regulating the balance of the 
fibrinolysis system.

Copyright © 2021 Elsevier B.V. All rights reserved.

DOI: 10.1016/j.jep.2021.114177
PMID: 33945856 [Indexed for MEDLINE]


5. Zhongguo Zhong Yao Za Zhi. 2018 Apr;43(8):1667-1674. doi: 
10.19540/j.cnki.cjcmm.20180224.001.

[Study on quality evaluation of Dihuang (Rehmannia glutinosa) by two-dimension 
HPLC fingerprints and chemometrics methods].

[Article in Chinese]

Huang CY(1), Ouyang DW(1), Niu LX(1), Zhou J(1), Lin S(1), Hu X(1).

Author information:
(1)Innovation Center of Chinese Medicine， China State Institute of 
Pharmaceutical Industry， Shanghai 201203， China.

The study is to establish the two-dimension HPLC fingerprints of Dihuang 
(Rehmannia glutinosa), by HPLC-PDA and HPLC-ELSD methods. The separations were 
performed on Waters Atlantis®T3（4.6 mm× 250 mm，5 μm）and Welch 
Ultimate®Hilic-NH₂（4.6 mm× 250 mm，5 μm）columns with the gradient elution of 
acetonitrile-0.01% phosphoric acid and acetonitrile-water, respectively. The 
chromatographic display wavelength for PDA detector was set at 203 nm. For 
HPLC-ELSD, the nebulizer was set as cooling mode, the drift tube temperature was 
set at 60 °C and the gas pressure was 35.0 psi. Based on similarity evaluation 
system for chromatographic fingerprint of traditional Chinese medicine, 26 and 
10 chromatographic peaks were determined as common components for HPLC-PDA and 
HPLC-ELSD fingerprints, respectively. Chemometrics analyses, such as similarity 
analysis; cluster analysis and principal component analysis, were performed on 
the common peak areas in two-dimension fingerprints for 41 batches of Dihuang 
from multiple sources. The results showed that the HPLC-PDA fingerprint could 
distinguish dried rehmannia root between different sources, and HPLC-ELSD 
fingerprint could differentiate dried rehmannia root from prepared rehmannia 
root. The two-dimension fingerprints were established with advantages of a good 
degree of separation, abundant chemical information and multi-components 
identified including two nucleosides (adenosine and uridine)，four iridoid 
glycosides (catalpa alcohol，rehmaionoside D，rehmaionoside A and leonuride)，two 
phenylethanoid glycosides (acteoside and cistanoside A) and nine sugars. The 
method is simple and practical, which could be used for the identification and 
quality assessment for Dihuang.

Copyright© by the Chinese Pharmaceutical Association.

DOI: 10.19540/j.cnki.cjcmm.20180224.001
PMID: 29751715 [Indexed for MEDLINE]

Conflict of interest statement: The authors of this article and the planning 
committee members and staff have no relevant financial relationships with 
commercial interests to disclose.