Psychoactive Plant Database - Neuroactive Phytochemical Collection

1. Phytomedicine. 2023 Dec;121:155093. doi: 10.1016/j.phymed.2023.155093. Epub
2023  Sep 17.

Salvianolic acid F suppresses KRAS-dependent lung cancer cell growth through the 
PI3K/AKT signaling pathway.

Hou X(1), Zhou C(2), Liang Z(2), Qiu H(2), Zhou Z(2), Zheng H(2), Li Z(3), Wang 
Y(2), Qi X(2), Lu L(4), Cao Y(5), Zheng J(6).

Author information:
(1)Joint Laboratory for Translational Cancer Research of Chinese Medicine of the 
Ministry of Education of the People's Republic of China, Guangdong-Hong 
Kong-Macau Joint Lab on Chinese Medicine and Immune Disease Research, 
International Institute for Translational Chinese Medicine, Guangzhou University 
of Chinese Medicine, Guangzhou, Guangdong 510006, China; The First Affiliated 
Hospital, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510405, 
China; The First Clinical Medical School, Guangzhou University of Chinese 
Medicine, Guangzhou, Guangdong 510405, China.
(2)Joint Laboratory for Translational Cancer Research of Chinese Medicine of the 
Ministry of Education of the People's Republic of China, Guangdong-Hong 
Kong-Macau Joint Lab on Chinese Medicine and Immune Disease Research, 
International Institute for Translational Chinese Medicine, Guangzhou University 
of Chinese Medicine, Guangzhou, Guangdong 510006, China.
(3)The First Affiliated Hospital, Guangzhou University of Chinese Medicine, 
Guangzhou, Guangdong 510405, China; The First Clinical Medical School, Guangzhou 
University of Chinese Medicine, Guangzhou, Guangdong 510405, China.
(4)Joint Laboratory for Translational Cancer Research of Chinese Medicine of the 
Ministry of Education of the People's Republic of China, Guangdong-Hong 
Kong-Macau Joint Lab on Chinese Medicine and Immune Disease Research, 
International Institute for Translational Chinese Medicine, Guangzhou University 
of Chinese Medicine, Guangzhou, Guangdong 510006, China. Electronic address: 
lllu@gzucm.edu.cn.
(5)The First Affiliated Hospital, Guangzhou University of Chinese Medicine, 
Guangzhou, Guangdong 510405, China; The First Clinical Medical School, Guangzhou 
University of Chinese Medicine, Guangzhou, Guangdong 510405, China. Electronic 
address: caoyang0342@gzucm.edu.cn.
(6)Joint Laboratory for Translational Cancer Research of Chinese Medicine of the 
Ministry of Education of the People's Republic of China, Guangdong-Hong 
Kong-Macau Joint Lab on Chinese Medicine and Immune Disease Research, 
International Institute for Translational Chinese Medicine, Guangzhou University 
of Chinese Medicine, Guangzhou, Guangdong 510006, China. Electronic address: 
20212110030@stu.gzucm.edu.cn.

BACKGROUND: KRAS mutation is a common driver of NSCLC, and there is a high 
proportion of lung cancer patients with KRAS G12C and G12D mutation. KRAS was 
previously considered an "undruggable" target, but the first KRAS G12C 
mutation-targeted drug AMG510, entered the market in 2021. However, treatments 
for G12D mutant tumors remain to be discovered. Salvianolic acid F (SalF), a 
monomer derived from the traditional Chinese medicine Salvia miltiorrhiza (SM), 
and KRAS had high binding affinity, especially for KRAS G12D. There is an urgent 
need to investigate effective and safe novel targeted therapies against KRAS 
G12D-driven NSCLC.
METHODS: To evaluate the anticancer effect of SalF, we used KRAS-overexpressing 
lung cancer cells in vitro, a subcutaneous transplant tumor model, and KRAS G12D 
mice model in vivo. Then, the binding effect of SalF and KRAS was investigated 
using molecular docking, proteolytic assays and protein thermal shift assays. 
More critically, the PI3K/AKT signaling pathway in the lung was investigated 
utilizing RT-qPCR and Western Blotting.
RESULTS: This is the first study to evaluate the anticancer effect of SalF on 
KRAS-overexpressing lung cancer cells or KRAS G12D lung tumors in vivo. We 
demonstrated that SalF inhibits OE-KRAS A549 cell migration, proliferation and 
promotes apoptosis in vitro. In addition, we used a subcutaneous transplant 
tumor model to show that SalF suppresses the growth of lung cancer cells in 
vivo. Interestingly, our group found that SalF was strongly bound to G12D and 
could decrease the stability and promoted the degradation of the KRAS G12D 
mutant through molecular docking, proteolytic assays and protein thermal shift 
assays. Further research demonstrated that in the KrasG12D mice model, after 
SalF treatment, the number and size of mouse lung tumors were significantly 
reduced. More importantly, SalF can promote apoptosis by inhibiting downstream 
PI3K/AKT signaling pathway activation.
CONCLUSION: SalF activated apoptosis signaling pathways, suppressed 
anti-apoptotic genes, and inhibited lung cancer cell growth. These datas 
suggested that SalF could effectively inhibit the growth of lung tumors with 
KRAS G12D mutation. SalF may be a novel inhibitor against KRAS G12D, providing a 
strong theoretical basis for the clinical treatment of lung cancer with KRAS 
mutations.

Copyright © 2023. Published by Elsevier GmbH.

DOI: 10.1016/j.phymed.2023.155093
PMID: 37783131 [Indexed for MEDLINE]

Conflict of interest statement: Declaration of Competing Interest All 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.


2. J Ethnopharmacol. 2023 Nov 15;316:116698. doi: 10.1016/j.jep.2023.116698. Epub
 2023 Jun 5.

Porcine cardiac blood - Salvia miltiorrhiza root alleviates cerebral ischemia 
reperfusion injury by inhibiting oxidative stress induced apoptosis through 
PI3K/AKT/Bcl-2/Bax signaling pathway.

Zhou S(1), Gao X(2), Chen C(2), Zhang J(3), Zhang Y(4), Zhang L(5), Yan X(6).

Author information:
(1)Changzhou Key Laboratory of Human Use Experience Research & Transformation of 
Menghe Medical Sect, Changzhou Hospital of Chinese Medicine Affiliated to 
Nanjing University of Chinese Medicine, No. 25 Heping North Road, Tianning 
District, Changzhou, 213003, PR China; Jiangsu Key Laboratory for High 
Technology Research of TCM Formulae, National and Local Collaborative 
Engineering Center of Chinese Medicinal Resources Industrialization and Formulae 
Innovative Medicine and Jiangsu Collaborative Innovation Center of Chinese 
Medicinal Resources Industrialization, Nanjing University of Chinese Medicine, 
No.138, Xianlin Road, Qixia District, Nanjing, 210023, PR China.
(2)Jiangsu Key Laboratory for High Technology Research of TCM Formulae, National 
and Local Collaborative Engineering Center of Chinese Medicinal Resources 
Industrialization and Formulae Innovative Medicine and Jiangsu Collaborative 
Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing 
University of Chinese Medicine, No.138, Xianlin Road, Qixia District, Nanjing, 
210023, PR China.
(3)Changzhou Key Laboratory of Human Use Experience Research & Transformation of 
Menghe Medical Sect, Changzhou Hospital of Chinese Medicine Affiliated to 
Nanjing University of Chinese Medicine, No. 25 Heping North Road, Tianning 
District, Changzhou, 213003, PR China.
(4)Jiangsu Key Laboratory for High Technology Research of TCM Formulae, National 
and Local Collaborative Engineering Center of Chinese Medicinal Resources 
Industrialization and Formulae Innovative Medicine and Jiangsu Collaborative 
Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing 
University of Chinese Medicine, No.138, Xianlin Road, Qixia District, Nanjing, 
210023, PR China. Electronic address: zhangyi@njucm.edu.cn.
(5)Jiangsu Key Laboratory for High Technology Research of TCM Formulae, National 
and Local Collaborative Engineering Center of Chinese Medicinal Resources 
Industrialization and Formulae Innovative Medicine and Jiangsu Collaborative 
Innovation Center of Chinese Medicinal Resources Industrialization, Nanjing 
University of Chinese Medicine, No.138, Xianlin Road, Qixia District, Nanjing, 
210023, PR China. Electronic address: zhangli@njucm.edu.cn.
(6)Changzhou Key Laboratory of Human Use Experience Research & Transformation of 
Menghe Medical Sect, Changzhou Hospital of Chinese Medicine Affiliated to 
Nanjing University of Chinese Medicine, No. 25 Heping North Road, Tianning 
District, Changzhou, 213003, PR China. Electronic address: 
yanxiaojing963@163.com.

ETHNOPHARMACOLOGICAL RELEVANCE: Salvia miltiorrhiza Bge. mixed with porcine 
cardiac blood (PCB-DS) is mainly employed for the treatment of brain 
ischemia-induced mental disturbances, palpitations and phlegm confusion based on 
the traditional principle of Menghe medical sect. PCB is the guide to DS and 
enhances the effect of DS. However, the potential mechanism of PCB-DS preventing 
cerebral ischemia/reperfusion injury (CIRI) from the perspective of oxidative 
stress induced cell apoptosis remains unknown.
AIM OF THE STUDY: To investigate the pharmacological activity and molecular 
mechanism of PCB-DS against CIRI.
MATERIALS AND METHODS: DS samples processed with different methods were prepared 
and UPLC-Q-TOF-MS/MS was employed for qualitative analysis of the respective 
processing product. The middle cerebral artery occlusion reperfusion model was 
then established to investigate the pharmacological activities of PCB-DS. 
Pathological changes in the rat brain were observed by triphenyl tetrazolium 
chloride (TTC), hematoxylin-eosin, and TUNEL staining. The levels of IL-6, 
IL-1β, and TNF-α were detected by ELISA to evaluate the inflammatory damage. 
Metabolomics of cerebrospinal fluid was further used to explore the potential 
mechanism of PCB-DS in preventing CIRI. Based on this, the levels of oxidative 
stress-related lactate dehydrogenase (LDH), reactive oxygen species (ROS), 
malondialdehyde (MDA), and superoxide dismutase (SOD) were determined. The 
protein levels of PI3K, AKT, Bcl-2, Bax, cleaved-caspase-3, and 
cleaved-caspase-9 proteins of the cerebral infarct zone were finally measured by 
western blotting.
RESULTS: Forty-seven components were identified in four processing products. 
Compared to DS, the content of total aqueous components in PCB-DS was 
significantly increased including salvianolic acid B isomer, salvianolic acid D, 
salvianolic acid F, and salvianolic acid H/I/J. Among the DS, DS processed with 
wine, DS processed with pig blood, and DS processed with porcine cardiac blood, 
PCB-DS best alleviated the CIRI through the neurological score, brain infarct 
volume, brain histopathology and the levels of inflammatory factors in the 
brain. Twenty-five significant metabolites in the cerebrospinal fluid were 
screened out between the sham and I/R groups. They were mainly involved in the 
beta-alanine metabolism, histidine metabolism, and lysine degradation, which 
indicated that PCB-DS may inhibit oxidative stress-induced apoptosis to achieve 
treating ischemic stroke. The results of biomedical examination showed that 
PCB-DS could alleviate oxidative damage, significantly downregulate the 
expression of Bax, cleaved caspase-3 and cleaved caspase-9, and upregulate the 
expression of p-PI3K, p-AKT, and Bcl-2.
CONCLUSION: In summary, this study demonstrated that PCB-DS alleviated CIRI and 
the molecular mechanism may be related to inhibiting the oxidative stress 
induced apoptosis through PI3K/AKT/Bcl-2/Bax signaling pathway.

Copyright © 2023 Elsevier B.V. All rights reserved.

DOI: 10.1016/j.jep.2023.116698
PMID: 37286116 [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 Orofac Orthop. 2022 Oct;83(Suppl 1):85-95. doi: 10.1007/s00056-021-00366-3. 
Epub 2022 Jan 11.

New bone-generative effect of Salvia officinalis L. in the expanded midpalatal 
suture : An in vivo and in vitro study.

[Article in English]

Kayalar E(1)(2)(3), Goger F(4), Tas Deynek G(5), Tok OE(6), Kucuk S(7).

Author information:
(1)Department of Orthodontics, Faculty of Dentistry, Istanbul Aydin University, 
34295, Florya, Istanbul, Turkey. emrekayalar@aydin.edu.tr.
(2)Discipline of Orthodontics and Paediatric Dentistry, School of Dentistry, The 
University of Sydney, Sydney Dental Hospital, Surry Hills, Australia. 
emrekayalar@aydin.edu.tr.
(3)Department of Pharmaceutical Botany, Faculty of Pharmacy, Anadolu University, 
Eskisehir, Turkey. emrekayalar@aydin.edu.tr.
(4)Department of Pharmacognosy, Faculty of Pharmacy, Anadolu University, 
Eskisehir, Turkey.
(5)Private Practice, Istanbul, Turkey.
(6)Department of Histology and Embryology, Faculty of Medicine, Regenerative and 
Restorative Medicine Research Center (REMER), Istanbul Medipol University, 
Istanbul, Turkey.
(7)Department of Pharmaceutical Botany, Faculty of Pharmacy, Anadolu University, 
Eskisehir, Turkey.

PURPOSE: The aims of this study were to evaluate the effects of systemic 
administration of Salvia officinalis Linnaeus (L.) leaf extract on new bone 
formation in the expanded premaxillary suture in rats in vivo and to examine the 
antioxidant effects and phenolic profile of Salvia officinalis (SO) leaf and 
root extracts in vitro.
METHODS: Fourteen male Sprague Dawley rats were allocated to two groups: SO 
group (n = 7) and control group (n = 7). An open-loop spring was attached to the 
upper incisors of each rat to expand the premaxillae. A 5-day expansion period 
followed by a 12-day retention period was observed. The rats in the SO group 
received systemic administration of 20 mg SO/kg/day via the orogastric route for 
17 days. Histomorphometric examinations were carried out to examine the amount 
of new bone formation, number of capillaries, and intensity of inflammatory cell 
response. Immunohistochemical analysis was conducted to examine the number of 
osteoblasts and osteoclasts. Leaf and root extracts of SO were also analyzed for 
antioxidant activity and phenolic compounds in vitro.
RESULTS: Statistical analysis showed that the following were higher in the SO 
group than in the control group: new bone formation, number of osteoblasts and 
osteoclasts, intensity of inflammatory cell response (neutrophils, lymphocytes, 
and macrophages), and number of capillaries. The major compound identified in SO 
leaf extract was rosmarinic acid, while luteolin derivatives, salvianolic 
acid F, and medioresinol were also present.
CONCLUSIONS: Salvia officinalis L. from leaf extract provided antioxidant 
effects and stimulated enhanced new bone formation in the expanded midpalatal 
suture after maxillary expansion in rats.

Publisher: ZUSAMMENFASSUNG: ZIELSETZUNG: Ziele dieser Studie waren die Bewertung 
der Auswirkungen einer systemischen Verabreichung von Salvia 
officinalis Linnaeus (L.) auf die Knochenneubildung in der erweiterten 
prämaxillären Naht bei Ratten unter In-vivo-Bedingungen sowie die Untersuchung 
der antioxidativen Wirkungen und des phenolischen Profils von Salvia 
officinalis(SO)-Extrakten unter In-vitro-Bedingungen.
METHODEN: Vierzehn männliche Sprague-Dawley-Ratten wurden 2 Gruppen zugeordnet: 
SO- (n = 7) und Kontrollgruppe (n = 7). An den oberen Schneidezähnen jeder Ratte 
wurde eine offene Feder zur prämaxillären Erweiterung angebracht. Untersucht 
wurden eine 5‑tägige Expansionsperiode, gefolgt von einer 12-tägigen 
Retentionsdauer. Den Ratten in der SO-Gruppe wurde 17 Tage lang 20 mg SO/kg/Tag 
über eine orogastrale Sonde verabreicht. Histomorphometrische Untersuchungen 
wurden durchgeführt, um die Menge der Knochenneubildung, die Anzahl der 
Kapillaren und die Intensität der Entzündungszellen zu ermitteln, ferner eine 
immunhistochemische Analyse, um die Anzahl der Osteoblasten und Osteoklasten zu 
bestimmen. Blatt- und Wurzelextrakte von SO wurden zudem in vitro auf 
antioxidative Aktivität und phenolische Verbindungen analysiert.
ERGEBNISSE: Die statistische Analyse hat gezeigt, dass die Knochenneubildung, 
die Anzahl der Osteoblasten und Osteoklasten, die Intensität der 
Entzündungszellen sowie die Anzahl der Kapillaren in der SO-Gruppe höher waren 
als in der Kontrollgruppe. Die wichtigste im SO-Blattextrakt identifizierte 
Verbindung war Rosmarinsäure, zusätzlich waren Luteolinderivate, 
Salvianolsäure F und Medioresinol nachweisbar.
SCHLUSSFOLGERUNG: Der Salvia-officinalis-L.-Blattextrakt hatte antioxidative 
Wirkungen und stimulierte die erhöhte Knochenneubildung in der erweiterten 
mittleren Gaumennaht nach Expansion des Oberkiefers bei Ratten.

© 2022. Springer Medizin Verlag GmbH, ein Teil von Springer Nature.

DOI: 10.1007/s00056-021-00366-3
PMID: 35015090 [Indexed for MEDLINE]


4. Pharm Biol. 2021 Dec;59(1):242-251. doi: 10.1080/13880209.2020.1870506.

Evaluation of the anti-inflammatory and antioxidant pharmcodynamic compoents of 
naoxintong capsules as a basis of broad spectrum effects.

Lv B(1), Deng L(1), Xie T(1), Wei X(1), Liu X(1), Tan W(1), Wang X(1)(2), Gao 
X(1).

Author information:
(1)State Key Laboratory of Modern Chinese Medicine, Tianjin University of 
Traditional Chinese Medicine, Tianjin, China.
(2)College of Traditional Chinese Medicine, Tianjin University of Traditional 
Chinese Medicine, Tianjin, China.

CONTEXT: Naoxintong capsule (NXT) is one of the most prevalent Traditional 
Chinese Medicine formulations in the treatment of coronary heart disease (CHD), 
yet the action of pharmacodynamic components remains unclear.
OBJECTIVE: To determine the basis by which pharmacodynamic components of NXT may 
be effective in the treatment of CHD.
MATERIALS AND METHODS: The protective effect of NXT (0.01-100 μg/mL) on 293 T 
and hy926 cells was determined by MTT assay for 24 h. Afterwards, to investigate 
the pharmacodynamic material basis of NXT in anti-inflammatory and antioxidant 
effects, based on previous UPLC/Q-TOF analysis, 293 T and hy926 cells were 
divided into control (treated with solvent), model (incubated with TNF-α, LPS or 
H2O2), intervention (treated with UPLC components) and positive groups. After 24 
h of treatment, all cells were tested to verify the screening results. MOE 
software was applied to dock bioactive compounds with phosphoinositide 3-kinase 
(PI3K), then the protein expression and phosphate levels were determined by 
western blotting.
RESULTS: NXT could significantly inhibit the expression of NF-κB, MMP-9 and NO 
in cells with IC50 values of 0.1178, 0.1182 and 0.1094 μg/mL. Based on the 
screening results, six components of NXT were identified (calycosin, ferulic 
acid, salvianolic acid B, ononin, salvianolic acid E, and salvianolic acid F) 
which can inhibit NF-κB, MMP-9, and NO simultaneously, while exerting 
cytoprotective effects by inhibiting the activation of the PI3K/AKT pathway 
under different conditions by virtue of their advantageous interaction with 
PI3K.
CONCLUSIONS: These ingredients have outstanding therapeutic potential and may 
provide a scientific basis for the future application and research of NXT.

DOI: 10.1080/13880209.2020.1870506
PMCID: PMC8079059
PMID: 33874833 [Indexed for MEDLINE]

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


5. Metabolites. 2020 Dec 3;10(12):497. doi: 10.3390/metabo10120497.

Phytochemical Profile and Antioxidant Activity of Aerial and Underground Parts 
of Salvia bulleyana Diels. Plants.

Grzegorczyk-Karolak I(1), Krzemińska M(1), Kiss AK(2), Olszewska MA(3), Owczarek 
A(3).

Author information:
(1)Department of Biology and Pharmaceutical Botany, Medical University of Lodz, 
90-151 Lodz, Poland.
(2)Department of Pharmacognosy and Molecular Basis of Phytotherapy, Medical 
University of Warsaw, 02-097 Warsaw, Poland.
(3)Department of Pharmacognosy, Medical University of Lodz, 90-151 Lodz, Poland.

Plants have been used for medical purposes since ancient times. However, a 
detailed analysis of their biological properties and their associated active 
compounds is needed to justify their therapeutic use in modern medicine. The aim 
of the study was to identify and quantify the phenolics present in 
hydromethanolic extracts of the roots and shoots of the Chinese Salvia species, 
Salvia bulleyana. The qualitative and quantitative analyses were carried out by 
ultrahigh-performance liquid chromatography with electrospray ionization mass 
spectrometry detection (UHPLC-PDA-ESI-MS), and high-performance liquid 
chromatography with photodiode array (HPLC-PDA) detection. The extracts of S. 
bulleyana were also screened for their antioxidant activity using ferric ion 
(Fe3+) reducing antioxidant power (FRAP), 1,1-diphenyl-2-picrylhydrazyl (DPPH), 
diammonium 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonate) cation (ABTS), 
superoxide radical anion (O2•-), and inhibition of lipid peroxidation assays. 
The S. bulleyana extracts were found to contain 38 substances, of which 36 were 
phenols, with a total level of 14.4 mg/g DW (dry weight) in shoots, and 
23.1 mg/g DW in roots. Twenty-eight phenols were polyphenolic acids or their 
derivatives, the most abundant in shoots being rosmarinic acid, and in roots, 
salvianolic acid K followed by rosmarinic acid. The other major phenolic acids 
were caffeic acid, caffeoyl-threonic acids, isomers of lithospermic acid, 
salvianolic acid F, salvianolic acid B, and yunnaneic acid E. In addition to 
polyphenolic acids, nine flavonoids were detected in the shoot extract. While 
both extracts showed significant antioxidant activity, the shoot extract, 
containing both polyphenolic acids and flavonoids, demonstrated a slightly 
greater antioxidant potential in some of the anti-radical tests than the roots. 
However, the root extract proved to be slightly more effective in the lipid 
peroxidation inhibition test. Thus, S. bulleyana was demonstrated as a promising 
source of antioxidants, and worthy of further more detailed studies.

DOI: 10.3390/metabo10120497
PMCID: PMC7761800
PMID: 33287467

Conflict of interest statement: The authors declare no conflict of interest.