Psychoactive Plant Database - Neuroactive Phytochemical Collection

1. Antimicrob Agents Chemother. 2024 Oct 8;68(10):e0095924. doi: 
10.1128/aac.00959-24. Epub 2024 Aug 22.

Deoxyshikonin: a promising lead drug grass against drug resistance or 
sensitivity to Helicobacter pylori in an acidic environment.

Xu J-y(1), Dong H-h(1), Liao L-j(1), Yang S-x(2)(3), Wang L-y(1), Chen H(4), Luo 
P(5), Huang L(1), Guan A-x(2)(3), Huang Y-Q(2)(3)(6).

Author information:
(1)Guangxi Technology Innovation Cooperation Base of Prevention and Control 
Pathogenic Microbes with Drug Resistance, Youjiang Medical University for 
Nationalities, Baise, China.
(2)Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, 
China.
(3)Guangxi Zhuang Autonomous Region Engineering Research Center of Clinical 
Prevention and Control Technology and Leading Drug for Microorganisms with Drug 
Resistance in Border Ethnic Areas, Baise, China.
(4)Department of Pathology, School of Basic Medical Sciences, Wannan Medical 
College, Wuhu, China.
(5)Department of Gastroenterology, Wujin People's Hospital affiliated to JiangSu 
University, Changzhou, China.
(6)Guangxi Clinical Medical Research Center for Hepatobiliary Diseases, Liuzhou, 
China.

Helicobacter pylori (H. pylori) is closely associated with the diseases such as 
gastric sinusitis, peptic ulcers, and gastric adenocarcinoma. Its drug 
resistance is very severe, and new antibiotics are urgently needed. Nine comfrey 
compounds were screened by antimicrobial susceptibility testing, among which 
deoxyshikonin had the best inhibitory effect, with a minimum inhibitory 
concentration (MIC) of 0.5-1 µg/mL. In addition, deoxyshikonin also has a good 
antibacterial effect in an acidic environment, it is highly safe, and H. pylori 
does not readily develop drug resistance. Through in vivo experiments, it was 
proven that deoxyshikonin (7 mg/kg) had a beneficial therapeutic effect on acute 
gastritis in mice infected with the multidrug-resistant H. pylori BS001 strain. 
After treatment with desoxyshikonin, colonization of H. pylori in the gastric 
mucosa of mice was significantly reduced, gastric mucosal damage was repaired, 
inflammatory factors were reduced, and the treatment effect was better than that 
of standard triple therapy. Therefore, deoxyshikonin is a promising lead drug to 
solve the difficulty of drug resistance in H. pylori, and its antibacterial 
mechanism may be to destroy the biofilm and cause an oxidation reaction.

DOI: 10.1128/aac.00959-24
PMCID: PMC11460997
PMID: 39171918 [Indexed for MEDLINE]

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


2. Environ Toxicol. 2024 Sep;39(9):4308-4317. doi: 10.1002/tox.24323. Epub 2024
May  8.

Deoxyshikonin triggers apoptosis in cervical cancer cells through p38 
MAPK-mediated caspase activation.

Lee CY(1)(2), Chen PN(3)(4), Kao SH(3)(4), Wu HH(5), Hsiao YH(6)(7)(8), Huang 
TY(3)(4), Wang PH(3)(9), Yang SF(3)(4).

Author information:
(1)Department of Obstetrics and Gynecology, Chiayi Chang Gung Memorial Hospital, 
Chiayi, Taiwan.
(2)Department of Nursing, Chang Gung University of Science and Technology, 
Chiayi, Taiwan.
(3)Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
(4)Department of Medical Research, Chung Shan Medical University Hospital, 
Taichung, Taiwan.
(5)Program for Cancer Biology and Drug Discovery, China Medical University, 
Taichung, Taiwan.
(6)School of Medicine, Chung Shan Medical University, Taichung, Taiwan.
(7)Department of Obstetrics and Gynecology, Changhua Christian Hospital, 
Changhua, Taiwan.
(8)Women's Health Research Laboratory, Changhua Christian Hospital, Changhua, 
Taiwan.
(9)Department of Obstetrics and Gynecology, Chung Shan Medical University 
Hospital, Taichung, Taiwan.

Deoxyshikonin (DSK) is a biological component derived from Lithospermum 
erythrorhizon. Although DSK possesses potential anticancer activities, whether 
DSK exerts anticancer effects on cervical cancer cells is incompletely explored. 
This study was aimed to investigate the anticancer activity of DSK against 
cervical cancer cells and its molecular mechanisms. Cell viability was evaluated 
by MTT assay. Level of phosphorylation and protein was determined using Western 
blot. Involvement of signaling kinases was assessed by specific inhibitors. Our 
results revealed that DSK reduced viability of human cervical cell in a 
dose-dependent fashion. Meanwhile, DSK significantly elicited apoptosis of HeLa 
and SiHa cells. Apoptosis microarray was used to elucidate the involved 
pathways, and the results showed that DSK dose-dependently diminished cellular 
inhibitor of apoptosis protein 1 (cIAP1), cIAP2, and XIAP, and induced cleavage 
of poly(ADP-ribose) polymerase (PARP) and caspase-8/9/3. Furthermore, we 
observed that DSK significantly triggered activation of ERK, JNK, and p38 MAPK 
(p38), and only inhibition of p38 diminished the DSK-mediated pro-caspases 
cleavage. Taken together, our results demonstrate that DSK has anti-cervical 
cancer effects via the apoptotic cascade elicited by downregulation of IAPs and 
p38-mediated caspase activation. This suggests that DSK could act as an adjuvant 
to facilitate cervical cancer management.

© 2024 Wiley Periodicals LLC.

DOI: 10.1002/tox.24323
PMID: 38717057 [Indexed for MEDLINE]


3. Chem Biodivers. 2024 Apr;21(4):e202301946. doi: 10.1002/cbdv.202301946. Epub 
2024 Mar 18.

Effects of Naphthoquinones from the Roots of Onosma Armeniacum Klokov on Wound 
Healing.

Küpeli Akkol E(1), Subaş T(2), Özgen U(2), Süntar I(1), Ilhan M(3), Keleş H(4).

Author information:
(1)Department of Pharmacognosy, Faculty of Pharmacy, Gazi University, Ankara, 
06330, Türkiye.
(2)Department of Pharmacognosy, Faculty of Pharmacy, Karadeniz Technical 
University, 61080, Trabzon, Türkiye.
(3)Department of Pharmacognosy, Faculty of Pharmacy, Düzce University, Düzce, 
81620, Türkiye.
(4)Department of Pathology, Faculty of Veterinary Medicine, Afyon Kocatepe 
University, 03200, Afyonkarahisar, Türkiye.

In Turkish folk medicine, the roots of Onosma armeniacum Klokov are used to heal 
wounds, burns, hemorrhoids, hoarseness, dyspnea, stomach ulcers, and abdominal 
aches. The objective was to evaluate the plant's ethnopharmacological 
applications using in vivo pharmacological experimental models. In vivo linear 
incision and circular excision the wound models were used to assess the wound 
healing activity along with histopathological investigation. The active 
component(s) were isolated and identified after being exposed to several 
chromatographic separation procedures on the primary extract. The 
n-hexane-dichloromethane mixture extract was subjected to chromatographic 
separation after the wound-healing activity was confirmed. Deoxyshikonin (1), 
β,β-dimethylacrylshikonin (2), α-methyl-n-butylshikonin (3), isovalerylshikonin 
(4), acetylshikonin (5), β-hydroxyisovalerylshikonin (6), and 
5,8-O-dimethylacetylshikonin (7) were identified as the structures of the 
isolated compounds. The efficacy of O. armeniacum to heal wounds was 
investigated in this study. Shikonin derivatives were identified as the primary 
active components of the roots by bioassay-guided fractionation and isolation 
procedures.

© 2024 Wiley‐VHCA AG, Zurich, Switzerland.

DOI: 10.1002/cbdv.202301946
PMID: 38433095 [Indexed for MEDLINE]


4. Sci Rep. 2023 Jul 14;13(1):11376. doi: 10.1038/s41598-023-38517-8.

Phytochemical profiling and cytotoxic potential of Arnebia nobilis root extracts 
against hepatocellular carcinoma using in-vitro and in-silico approaches.

Kiran A(1), Altaf A(2), Sarwar M(1), Malik A(1), Maqbool T(1), Ali Q(3).

Author information:
(1)Institute of Molecular Biology and Biotechnology, The University of Lahore, 
Lahore, 54300, Pakistan.
(2)Institute of Molecular Biology and Biotechnology, The University of Lahore, 
Lahore, 54300, Pakistan. awaisaltaf362@yahoo.com.
(3)Department of Plant Breeding and Genetics, Faculty of Agricultural Sciences, 
University of the Punjab, Lahore, Pakistan. saim1692@gmail.com.

Hepatocellular carcinoma is the fifth most prevalent cancer worldwide. The 
emergence of drug resistance and other adverse effects in available anticancer 
options are challenging to explore natural sources. The current study was 
designed to decipher the Arnebia nobilis (A. nobilis) extracts for detecting 
phytochemicals, in-vitro evaluation of antioxidative and cytotoxic potentials, 
and in-silico prediction of potent anticancer compounds. The phytochemical 
analysis revealed the presence of flavonoids, phenols, tannins, alkaloids, 
quinones, and cardiac glycosides, in the ethanol (ANE) and n-hexane (ANH) 
extracts of A. nobilis. ANH extract exhibited a better antioxidant potential to 
scavenge DPPH, nitric oxide and superoxide anion radicals than ANE extract, 
which showed better potential only against H2O2 radicals. In 24 h treatment, ANH 
extract revealed higher cytotoxicity (IC50 value: 22.77 µg/mL) than ANH extract 
(IC50 value: 46.74 µg/mL) on cancer (HepG2) cells without intoxicating the 
normal (BHK) cells using MTT assay. A better apoptotic potential was observed in 
ANH extract (49.10%) compared to ANE extract (41.35%) on HepG2 cells using the 
annexin V/PI method. GCMS analysis of ANH extract identified 35 phytocompounds, 
from which only 14 bioactive compounds were selected for molecular docking based 
on druggability criteria and toxicity filters. Among the five top scorers, 
deoxyshikonin exhibited the best binding affinities of - 7.2, - 9.2, - 7.2 and 
- 9.2 kcal/mol against TNF-α, TGF-βR1, Bcl-2 and iNOS, respectively, followed by 
ethyl cholate and 2-Methyl-6-(4-methylphenyl)hept-2-en-4-one along with their 
desirable ADMET properties. The phytochemicals of ANH extract could be used as a 
promising drug candidate for liver cancer after further validations.

© 2023. The Author(s).

DOI: 10.1038/s41598-023-38517-8
PMCID: PMC10349071
PMID: 37452082 [Indexed for MEDLINE]

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


5. J Cell Mol Med. 2023 Jun;27(11):1592-1602. doi: 10.1111/jcmm.17764. Epub 2023 
May 8.

Apoptotic effect and cell arrest of deoxyshikonin in human osteosarcoma cells 
through the p38 pathway.

Hsieh MC(1)(2), Hsieh YH(3)(4), Chou CH(3)(4), Yang JS(3)(4), Lu PW(5), Huang 
TY(3)(4), Yang SF(3)(4), Lu KH(6)(7).

Author information:
(1)School of Medical Laboratory and Biotechnology, Chung Shan Medical 
University, Taichung, Taiwan.
(2)Department of Clinical Laboratory, Chung Shan Medical University Hospital, 
Taichung, Taiwan.
(3)Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
(4)Department of Medical Research, Chung Shan Medical University Hospital, 
Taichung, Taiwan.
(5)Morrison Academy Taichung, Taichung, Taiwan.
(6)Department of Orthopedics, Chung Shan Medical University Hospital, Taichung, 
Taiwan.
(7)School of Medicine, Chung Shan Medical University, Taichung, Taiwan.

Osteosarcoma is the most common primary bone cancer that affects adolescents 
with early metastatic potential and drastically reduces their long-term survival 
rate if pulmonary metastases are detected at diagnosis. The natural 
naphthoquinol compound deoxyshikonin exhibits anticancer properties, so we 
hypothesized that it has an apoptotic effect on osteosarcoma U2OS and HOS cells 
and studied its mechanisms. After deoxyshikonin treatment, dose-dependent 
decreases in cell viability, induction of cell apoptosis and arrest in the 
sub-G1 phase of U2OS and HOS cells were observed. The increases in cleaved 
caspase 3 expression and the decreases in X-chromosome-linked IAP (XIAP) and 
cellular inhibitors of apoptosis 1 (cIAP-1) expressions after deoxyshikonin 
treatment in the human apoptosis array were identified in HOS cells, and 
dose-dependent expression changes of IAPs and cleaved caspase 3, 8 and 9 were 
verified by Western blotting in U2OS and HOS cells. Phosphorylation of 
extracellular signal-regulated protein kinases (ERK)1/2, c-Jun N-terminal 
kinases (JNK)1/2 and p38 expressions in U2OS and HOS cells was also increased by 
deoxyshikonin in a dose-dependent manner. Subsequently, cotreatment with 
inhibitors of ERK (U0126), JNK (JNK-IN-8) and p38 (SB203580) was performed to 
show that p38 signalling is responsible for deoxyshikonin-induced apoptosis in 
U2OS and HOS cells, but not via the ERK and JNK pathways. These discoveries 
demonstrate that deoxyshikonin may be a possible chemotherapeutic candidate to 
induce cell arrest and apoptosis by activating extrinsic and intrinsic pathways 
through p38 for human osteosarcoma.

© 2023 The Authors. Journal of Cellular and Molecular Medicine published by 
Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.

DOI: 10.1111/jcmm.17764
PMCID: PMC10243165
PMID: 37155410 [Indexed for MEDLINE]

Conflict of interest statement: The authors declare that there is no conflict of 
interest.