Exploring the potential of natural and synthetic neuroprotective steroids against neurodegenerative disorders: A literature review

Abstract

Neurodegeneration is a complex process, which leads to progressive brain damage due to loss of neurons. Despite exhaustive research, the cause of neuronal loss in various degenerative disorders is not entirely understood. Neuroprotective steroids constitute an important line of attack, which could play a major role against the common mechanisms associated with various neurodegenerative disorders like Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis. Natural endogenous steroids induce the neuroprotection by protecting the nerve cells from neuronal injury through multiple mechanisms, therefore the structural modifications of the endogenous steroids could be helpful in the generation of new therapeutically useful neuroprotective agents. The review article will keep the readers apprised of the detailed description of natural as well as synthetic neuroprotective steroids from the medicinal chemistry point of view, which would be helpful in drug discovery efforts aimed toward neurodegenerative diseases.

Activation of Adrenal Steroidogenesis and an Improvement of Mood Balance in Postmenopausal Females after Spa Treatment Based on Physical Activity

“…Sleep disturbance; 2. daytime sleepiness; 3. fatigue and exhaustion; 4. low productivity; 5. headache; 6. perspiration; 7. vertigo; 8. faint feeling; 9. vomiting and nausea after anger; 10. hot and cold flashes; 11. shivers, inner need; 12. inattention and lack of concentration; 13. irritability and short temper; 14. memory retention; 15. backbone, muscle, and joint pain; 16. heart palpitations, heart pain; The intensity of the symptoms was self-estimated by patients using a 4-level scale: 0 = no, 1 = mild, 2 = high, 3 = extreme. The total score (from the viewpoint of neurotic tendency) was interpreted as follows: Normal (0-11), Mildly neurotic (12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22) Highly neurotic (23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33), Extremely neurotic (>34). The somatic and psychosomatic disturbances were reflected in questions 1-11 and 12-22, respectively, while psychiatric symptoms were represented by questions 23-33.…”

“…The data from the FZ as reported by Siriani et al [13] showed increased mRNA expression of the genes needed for DHEAS production, such as steroidogenic acute regulatory protein, cholesterol desmolase (CYP11A1), steroid C17-hydroxylase-C17,20-lyase (CYP17A1), and type 2A1 steroid sulfotransferase (SULT2A1), as well as the upregulation of type 1 CRH receptors after 24 h treatment of FZ cells with CRH, CRH-related peptide urocortin or ACTH. The various adrenal steroids that have synthesis controlled by CRH and ACTH as well as their metabolites may operate as neuroactive [14], neuroprotective [15] and immunoprotective [6] substances, affecting the somatic, psychosomatic and psychiatric health of patients [16][17][18][19].…”

Effects of crocin in reducing DNA damage, inflammation, and oxidative stress in multiple sclerosis patients: A double‐blind, randomized, and placebo‐controlled trial

“…In recent years, many natural and synthetic drugs have been identified to affect processes such as oxidative stress to inhibit the neurodegenerative mechanisms underlying MS. In this context, it has been depicted that antioxidant molecules and compounds, which can reduce oxidative stress and free radicals, may be used as potential strategies against neurodegenerative diseases, particularly MS …”

“…The synergistic effects of these immunological responses in CNS and their signaling pathways are presented as critical factors in the progression of neuronal degradation and DNA fragmentation in MS. [15] In recent years, many natural and synthetic drugs have been identified to affect processes such as oxidative stress to inhibit the neurodegenerative mechanisms underlying MS. In this context, it has been depicted that antioxidant molecules and compounds, which can reduce oxidative stress and free radicals, may be used as potential strategies against neurodegenerative diseases, particularly MS. [16] Saffron is one of the natural remedies in traditional medicine being used for various purposes such as sedative, antidepressants, antispasmodic, in addition to the treatment of scarlet fever, chickenpox, colds, asthma, eye, and cardiovascular diseases, and also cancers. [17][18][19][20] The analysis of the chemical composition of saffron has shown that this medicinal plant contains a large number of active and potent biological compounds.…”

Evidence for effective structure‐based neuromodulatory effects of new analogues of neurosteroid allopregnanolone

“…These encouraging findings let us to investigate whether some of our ANS may optimally exert a neuroprotective action by preventing neuronal death without promoting the cell proliferation that usually represents an undesirable effect hampering the treatment of neurodegenerative processes in various pathological situations, including cancers. Therefore, we compared the ability of our ANS and AP to protect against oxidative stress‐induced neuronal death that is pivotally involved in the patho‐physiological mechanisms of various neurodegenerative disorders . Our results clearly showed that both O‐allyl ANS (BR351 and BR297) had notable advantages over AP with regard to the protection of SH‐SY5Y cells against oxidative stress‐induced death.…”