This study provides a narrative review of diterpenoid alkaloids (DAs), a family of extremely important natural products found predominantly in some species of Aconitum and Delphinium (Ranunculaceae). DAs have long been a focus of research attention due to their numerous intricate structures and diverse biological activities, especially in the central nervous system (CNS). These alkaloids originate through the amination reaction of tetra or pentacyclic diterpenoids, which are classified into three categories and 46 types based on the number of carbon atoms in the backbone structure and structural differences. The main chemical characteristics of DAs are their heterocyclic systems containing β-aminoethanol, methylamine, or ethylamine functionality. Although the role of tertiary nitrogen in ring A and the polycyclic complex structure are of great importance in drug-receptor affinity, in silico studies have emphasized the role of certain sidechains in C13, C14, and C8. DAs showed antiepileptic effects in preclinical studies mostly through Na⁺ channels. Aconitine (1) and 3-acetyl aconitine (2) can desensitize Na⁺ channels after persistent activation. Lappaconitine (3), N-deacetyllapaconitine (4), 6-benzoylheteratisine (5), and 1-benzoylnapelline (6) deactivate these channels. Methyllycaconitine (16), mainly found in Delphinium species, possesses an extreme affinity for the binding sites of α7 nicotinic acetylcholine receptors (nAChR) and contributes to a wide range of neurologic functions and the release of neurotransmitters. Several DAs such as bulleyaconitine A (17), (3), and mesaconitine (8) from Aconitum species have a drastic analgesic effect. Among them, compound 17 has been used in China for decades. Their effect is explained by increasing the release of dynorphin A, activating the inhibitory noradrenergic neurons in the β-adrenergic system, and preventing the transmission of pain messages by inactivating the Na⁺ channels that have been stressed. Acetylcholinesterase inhibitory, neuroprotective, antidepressant, and anxiolytic activities are other CNS effects that have been investigated for certain DAs. However, despite various CNS effects, recent advances in developing new drugs from DAs were insignificant due to their neurotoxicity.

Background: Malaria parasites have gradually developed resistance to commonly used antimalarial drugs. For decades, chloroquine was the most widely used drug to eradicate malaria. However, with the spread of chloroquine resistance, many countries have adopted combination therapies that utilize two drugs acting synergistically instead of monotherapy. In this study, the synergistic effect of chloroquine and the semipolar extract of Artemisia kopetdaghensis. Semipolar extract (SPE) was investigated in vivo through pathological and parasitological studies on mouse model. Methods: Sixty female Balb/c mice infected with the Plasmodium berghei (P. berghei) parasite were treated with different concentrations of the semipolar extract of Artemisia kopetdaghensis (SPE) according to the protocol. The mean percentage of parasitemia, the mean survival time of the mice, the serum levels of IFN-γ, IL-4, IL-17, and TGF-β, and the effects of the SPE on the kidney, spleen, and liver tissues were investigated and compared across different treatment groups. The data were analyzed using Bonferroni, ANOVA, and Tukey tests. Results: The semipolar extract of Artemisia kopetdaghensis (SPE) demonstrated better therapeutic effects in both synergistic and monotherapy conditions compared to chloroquine alone. The combination of chloroquine and SPE resulted in the lowest parasitemia rate, the highest percentage of parasite inhibition, and the longest average survival time. Pathological studies showed no signs of acute toxicity in the organs. Conclusions: This study demonstrated that using chloroquine in combination with Artemisia kopetdaghensis semipolar extract has synergistic effects in reducing parasitemia, enhancing the inhibitory effect on parasite growth and reproduction, and balancing the host immune system.