Psychoactive Plant Database - Neuroactive Phytochemical Collection

1. ACS Omega. 2024 Aug 18;9(34):36099-36113. doi: 10.1021/acsomega.4c00082. 
eCollection 2024 Aug 27.

Role of Alkannin in the Therapeutic Targeting of Protein-Tyrosine Phosphatase 1B 
and Aldose Reductase in Type 2 Diabetes: An In Silico and In Vitro Evaluation.

Saeed M(1), Shoaib A(2), Tasleem M(3), Al-Shammary A(4), Kausar MA(5), El Asmar 
Z(1), Abdelgadir A(1), Sulieman AME(1), Ahmed EH(6), Zahin M(7), Ansari IA(8).

Author information:
(1)Department of Biology, College of Sciences, University of Ha'il, P.O. Box 
2240, Ha'il 81451, Saudi Arabia.
(2)Department of Clinical Pharmacy, College of Pharmacy, Jazan University, P.O. 
Box 114, Jazan 45142, Saudi Arabia.
(3)Center for Global Health Research, Saveetha Medical College and Hospital, 
Chennai 602105, India.
(4)Department of Public Health, College of Public Health and Health Informatics, 
University of Ha'il, P.O. Box 2240, Ha'il 81451, Saudi Arabia.
(5)Department of Biochemistry, College of Medicine, University of Ha'il, P.O. 
Box 2240, Ha'il 81451, Saudi Arabia.
(6)University of Ha'il, Faculty of Medicine Anatomy Department, Ha'il, KSA, Ain 
Shams University, Faculty of Medicine Anatomy and Embryology Department, Cairo 
11566, Egypt.
(7)James Graham Brown Cancer Center, University of Louisville, Louisville, 
Kentucky 40202, United States.
(8)Department of Biosciences, Integral University, Lucknow 226026, India.

Alkannin is a plant-derived naphthoquinone that is isolated from the 
Boraginaceae family plants. In our previous studies, we found that shikonin, 
which is the R-enantiomer of alkannin, has potent antidiabetic activity by 
inhibiting the action of the aldose reductase (AR) enzyme and the 
protein-tyrosine phosphatase 1B (PTP1B). Therefore, in this study, we aim to 
explore the antidiabetic effect of alkannin targeting PTP1B and AR by employing 
in silico and in vitro techniques. For in silico, we used different parameters 
such as ADMET analysis, molecular docking, MD simulation, Root Mean Square 
Deviation (RMSD), protein-ligand mapping, and free binding energy calculation. 
The in vitro evaluation was done by assessing the inhibitory activity and enzyme 
kinetics of PTP1B and AR inhibition by alkannin. The in silico studies indicate 
that alkannin possesses favorable pharmacological properties and possesses 
strong binding affinity for diabetes target proteins. Hydrogen bonds (Val297, 
Ala299, Leu300, and Ser302) and hydrophobic interactions (Trp20, Val47, Tyr48, 
Trp79, Trp111, Phe122, Trp219, Val297, Cys298, Ala299, Leu300, and Leu301) are 
established by the compound, which potentially improves specificity and aids in 
the stabilization of the protein-ligand complex. The results from in vitro 
studies show a potent dose-dependent PTP1B inhibitory activity with an IC50 
value of 19.47 μM, and toward AR it was estimated at 22.77 μM. Thus, from the 
results it is concluded that a low IC50 value of alkannin for both PTP1B and AR 
along with favorable pharmacological properties and optimal intra-molecular 
interactions indicates its utilization as a potential drug candidate for the 
management of diabetes and its end complications.

© 2024 The Authors. Published by American Chemical Society.

DOI: 10.1021/acsomega.4c00082
PMCID: PMC11359625
PMID: 39220541

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


2. Molecules. 2024 Aug 20;29(16):3919. doi: 10.3390/molecules29163919.

β,β-Dimethylacrylalkannin, a Natural Naphthoquinone, Inhibits the Growth of 
Hepatocellular Carcinoma Cells by Modulating Tumor-Associated Macrophages.

Shen LS(1)(2), Lin Z(3), Gong RH(4), Lin YS(5), Qiao XF(1)(2), Hu QM(1)(2), Qin 
WH(1)(2), Chen S(4)(5)(6), Yang Y(1)(2), Chen GQ(4)(5)(6).

Author information:
(1)Chongqing Academy of Chinese Materia Medica, Chongqing 400065, China.
(2)Sichuan-Chongqing Joint Key Laboratory of Innovation of New Drugs of 
Traditional Chinese Medicine, Chongqing 400065, China.
(3)Southern Medical University of Hospital of Integrated Traditional Chinese 
Medicine and Western Medicine, Southern Medical University, Guangzhou 510515, 
China.
(4)Department of Food Science and Nutrition, The Hong Kong Polytechnic 
University, Hung Hom, Hong Kong 999077, China.
(5)State Key Laboratory of Chinese Medicine and Molecular Pharmacology 
(Incubation), The Hong Kong Polytechnic University Shenzhen Research Institute, 
Shenzhen 518057, China.
(6)Research Centre for Chinese Medicine Innovation, The Hong Kong Polytechnic 
University, Hung Hom, Hong Kong 999077, China.

Tumor-associated macrophages (TAMs) are pivotal in the tumor microenvironment 
(TME) of hepatocellular carcinoma (HCC), influencing various stages from 
initiation to metastasis. Understanding the role of TAMs in HCC is crucial for 
developing novel therapeutic strategies. Macrophages exhibit plasticity, 
resulting in M1 and M2 phenotypes, with M1 macrophages displaying antitumor 
properties and M2 macrophages promoting tumor progression. Targeting TAMs to 
alter their polarization could offer new avenues for HCC treatment. 
β,β-dimethylacrylalkannin (DMAKN), a natural naphthoquinone, has gained 
attention for its antitumor properties. However, its impact on TAMs modulation 
remains unclear. This study investigates DMAKN's modulation of TAMs and its 
anti-HCC activity. Using an in vitro model with THP-1 cells, we induced M1 
macrophages with LPS/IFN-γ and M2 macrophages with IL-4/IL-13, confirming 
polarization with specific markers. Co-culturing these macrophages with HCC 
cells showed that M1 cells inhibited HCC growth, while M2 cells promoted it. 
Screening for non-toxic DMAKN concentrations revealed its ability to induce M1 
polarization and enhance LPS/IFN-γ-induced M1 macrophages, both showing anti-HCC 
effects. Conversely, DMAKN suppressed IL-4/IL-13-induced M2 polarization, 
inhibiting M2 macrophages' promotion of HCC cell viability. In summary, DMAKN 
induces and enhances M1 polarization while inhibiting M2 polarization of 
macrophages, thereby inhibiting HCC cell growth. These findings suggest that 
DMAKN has the potential to regulate TAMs in HCC, offering promise for future 
therapeutic development.

DOI: 10.3390/molecules29163919
PMCID: PMC11357245
PMID: 39202998 [Indexed for MEDLINE]

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


3. Discov Med. 2024 Jun;36(185):1231-1240. doi:
10.24976/Discov.Med.202436185.113.

Inhibitory Effects and Mechanisms of the Novel Shikonin Derivative DMAKO-20 on 
Melanoma Metastasis and Invasion.

Zhou X(1), Huang J(2), Liu S(3), Cui J(4), Chen J(1).

Author information:
(1)Department of Dermatology, Shanghai Ninth People's Hospital, Shanghai Jiao 
Tong University School of Medicine, 200010 Shanghai, China.
(2)Department of Dermatology, Huashan Hospital, Fudan University School of 
Medicine, 200031 Shanghai, China.
(3)School of Environmental Science and Engineering, Shanghai Jiao Tong 
University, 200240 Shanghai, China.
(4)School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, 
200240 Shanghai, China.

BACKGROUND: Cutaneous melanoma is a malignant tumor with an increasing 
incidence, prone to recurrence and metastasis. This study aims to explore the 
effects and mechanisms of the novel shikonin derivative 5,8-dimethyl alkannin 
oxime derivative (DMAKO-20) on the metastasis and invasion of melanoma cells.
METHODS: The inhibitory effects of DMAKO-20 on the melanoma cell line A375 were 
investigated through Cell Counting Kit-8 (CCK-8), Transwell and angiogenesis 
experiments. Network pharmacology and Gene Ontology (GO)/Kyoto Encyclopedia of 
Genes and Genomes (KEGG) analyses were employed to explore potential sites and 
pathways involved in this process. Additionally, quantitative polymerase chain 
reaction (qPCR) and Western blot experiments were conducted before and after 
drug treatment to verify the expression trends of related pathways and proteins.
RESULTS: DMAKO-20 demonstrated selective inhibition of proliferation, invasion 
and migration of melanoma cells at low concentrations. The WNT pathway appears 
to be implicated in this process, as DMAKO-20 effectively attenuates its 
activation, consequently reducing matrix metalloproteinase 9 (MMP9) and Cellular 
Communication Network Factor 1 (CCN1)/cysteine-rich angiogenic inducer 61 
(CYR61) levels. Such modulation inhibits melanoma dissemination and invasion 
into other tissues.
CONCLUSION: DMAKO-20 exhibits the capability to suppress metastasis and invasion 
of melanoma cells, suggesting its potential for clinical application as an 
adjuvant therapy against melanoma.

DOI: 10.24976/Discov.Med.202436185.113
PMID: 38926109 [Indexed for MEDLINE]


4. Front Pharmacol. 2024 Jun 7;15:1376252. doi: 10.3389/fphar.2024.1376252. 
eCollection 2024.

Targeting pyruvate kinase M2 for the treatment of kidney disease.

Chen DQ(#)(1), Han J(#)(1)(2), Liu H(1), Feng K(1), Li P(3).

Author information:
(1)College of Life Sciences, Northwest University, Xi'an, Shaanxi, China.
(2)Department of Nephrology, Xi'an Chang'an District Hospital, Xi'an, Shaanxi, 
China.
(3)Beijing Key Lab for Immune-Mediated Inflammatory Diseases, Institute of 
Clinical Medical Sciences, China-Japan Friendship Hospital, Beijing, China.
(#)Contributed equally

Pyruvate kinase M2 (PKM2), a rate limiting enzyme in glycolysis, is a cellular 
regulator that has received extensive attention and regards as a metabolic 
regulator of cellular metabolism and energy. Kidney is a highly metabolically 
active organ, and glycolysis is the important energy resource for kidney. The 
accumulated evidences indicates that the enzymatic activity of PKM2 is disturbed 
in kidney disease progression and treatment, especially diabetic kidney disease 
and acute kidney injury. Modulating PKM2 post-translational modification 
determines its enzymatic activity and nuclear translocation that serves as an 
important interventional approach to regulate PKM2. Emerging evidences show that 
PKM2 and its post-translational modification participate in kidney disease 
progression and treatment through modulating metabolism regulation, podocyte 
injury, fibroblast activation and proliferation, macrophage polarization, and T 
cell regulation. Interestingly, PKM2 activators (TEPP-46, DASA-58, mitapivat, 
and TP-1454) and PKM2 inhibitors (shikonin, alkannin, compound 3k and compound 
3h) have exhibited potential therapeutic property in kidney disease, which 
indicates the pleiotropic effects of PKM2 in kidney. In the future, the deep 
investigation of PKM2 pleiotropic effects in kidney is urgently needed to 
determine the therapeutic effect of PKM2 activator/inhibitor to benefit 
patients. The information in this review highlights that PKM2 functions as a 
potential biomarker and therapeutic target for kidney diseases.

Copyright © 2024 Chen, Han, Liu, Feng and Li.

DOI: 10.3389/fphar.2024.1376252
PMCID: PMC11190346
PMID: 38910890

Conflict of interest statement: 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. Antibodies (Basel). 2024 May 7;13(2):38. doi: 10.3390/antib13020038.

Structural and Functional Characterization of Medicinal Plants as Selective 
Antibodies towards Therapy of COVID-19 Symptoms.

Mollaamin F(1).

Author information:
(1)Department of Biomedical Engineering, Faculty of Engineering and 
Architecture, Kastamonu University, Kastamonu 37150, Turkey.

Considering the COVID-19 pandemic, this research aims to investigate some herbs 
as probable therapies for this disease. Achillea millefolium (Yarrow), Alkanet, 
Rumex patientia (Patience dock), Dill, Tarragon, and sweet fennel, including 
some principal chemical compounds of achillin, alkannin, cuminaldehyde, 
dillapiole, estragole, and fenchone have been selected. The possible roles of 
these medicinal plants in COVID-19 treatment have been investigated through 
quantum sensing methods. The formation of hydrogen bonding between the principal 
substances selected in anti-COVID natural drugs and Tyr-Met-His (the database 
amino acids fragment), as the active area of the COVID protein, has been 
evaluated. The physical and chemical attributes of nuclear magnetic resonance, 
vibrational frequency, the highest occupied molecular orbital energy and the 
lowest unoccupied molecular orbital energy, partial charges, and spin density 
have been investigated using the DFT/TD-DFT method and 6-311+G (2d,p) basis set 
by the Gaussian 16 revision C.01 program toward the industry of drug design. 
This research has exhibited that there is relative agreement among the results 
that these medicinal plants could be efficient against COVID-19 symptoms.

DOI: 10.3390/antib13020038
PMCID: PMC11130808
PMID: 38804306

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