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104 Herbal Pharmacopeia
TABLE 5.6
Herbal Bioactive Compounds and Their Anticancer Mechanisms
S# Name of Compounds Bioactivity/Functions/Mechanisms/Properties Cell Line References
01 Alisol B acetate Induces apoptosis and Bax translocation via Bcl- 2
pathways.
02 6-gingerol, 6-paradol Suppressed cellular proliferation through apoptotic
mechanisms.
03 5-Fluorouracil Bak, Bad, Bcl- 2, Bax, and p53 protein Colon [166]
04 10-paradol,
6-dehydroparadol,
6-paradol
05 Allyl isothiocyanate
(AITC)
06 Alkaloid Inhibit the growth. Leukemia (Jurkat J6) [169]
07 Aloe- emodin DNA fragmentation, induced apoptosis, Bag- 1,
08 Anthocyanin Inhibit cancer cell growth Lung, colon, gastric,
09 Angelicin Increased cellular cytotoxicity, DNA fragmentation,
10 Apigenin Increased p53 accumulation, G2/M phase arrest,
11 Baicalein, a avonoid DNA fragmentation, induction apoptosis HL- 60 [174]
12 Berberine ROS, induces apoptosis, inhibition cell growth in
13 Chrysophanol Induces necrosis by generating ROS Liver (J5) [176]
14 Curcumin Activation caspase- 9, -3. up- regulate Bax, decrease
15 Gypenosides (Gyp) Inhibits NAT mRNA expression. Cervix (Ca Ski) [178]
16 Diallyl trisulde
(DATS)
17 Diosgenin and
hecogenin
18 Emodin DNA disintegration, arrest cell cycle, enhance
19 Flavonoid glycoside DNA fragmentation, anti- proliferative and
20 Fucoidans Anti- tumor activity. Melanoma, Colon. [182]
21 Fucoxanthin (FX) Induction of Gi arrest, induced GADD45A. Hepato (HepG2,
22 Gammalinolenic acid
23 Ganoderic acids
(GAs)
Caused proteolytic cleavage of pro- caspase- 3,
induced apoptosis.
Cyclin B1, control G2/M, reduce Bcl- 2 expression,
cell division cycle (Cdc- 25B, and Cdc- 25C).
Bcl- X(L), translocation of Bak, Bak expression,
activated caspase- 3, -8, -9, Bax.
up- regulation of caspase- 9, -3 activity, downregulate Mcl- 1, Bcl- 2, Bcl- xL, induced MAP
kinases/PI3K/ AKT/GSK- 3β, and caspase- 8
activity.
induce apoptosis, induction of p21 expression,
enhanced WAF1/p21 level through the p53dependent pathway.
G0/G1-phase, cellular DNA, Ca2+ production.
cyclin A, B, Cdk1, G2/M phase arrest, downregulation of Bcl- 2.
Induce apoptosis Gastric (BGC823) [179]
DNA fragmentation, induce apoptosis. Cervical (CaSki) [115]
caspase- 3, p53/21, Fas/APO- 1.
cytotoxicity effect.
Production of IL- 1β
Anti- angiogenesis and Cytotoxic mechanisms Cancer cell lines [185]
Prostate (PC- 3) [164]
Promyelocytic
(HL- 60)
Oral squamous (KB) [167]
Prostate (PC- 3,
LNCaP)
Lung (CH27) [170]
and breast.
Neuroblastoma
(SH- SY5Y)
Hepatoma (Hep G2,
Hep 3B, and PLC/
PRF/5).
Oral (HSC- 3) [175]
Nasopharyngeal
(NPC- TW 076)
Hepatoma(PRF/5/
PLC, HepC3A/G2,
and SK- HEP- 1)
Breast (A375, and
HL60)
DU145)
Monocytes [184]
[165]
[168]
[171]
[172]
[173]
[177]
[180]
[181]
[183]
(Continued)
Bioactive Compounds in Herbal Remedies 105
TABLE 5.6 (CONTINUED)
Herbal Bioactive Compounds and Their Anticancer Mechanisms
S# Name of Compounds Bioactivity/Functions/Mechanisms/Properties Cell Line References
24 Gallic acid Induced apoptosis, DNA fragmentation Stomach colon (Colo
205), and (KATO
III).
25 Ginseng saponin K Induced apoptotic morphology, caspase- 3, interfered
Bcl- 2.
26 Ginsenoside- Rb1 Estrogen- responsive luciferase reporter gene
activation.
27 Gossypol Cytotoxic activity Breast (HBL- 100),
28 HMJ- 30/quinazoline Enhance apoptosis, inhibit cell growth, caspase- 8,
-9, -3 pathways, DNA break.
29 Limonin Enhanced doxorubicin cytotoxicity, decreased P- gp
activity.
30 Peridinin Activating caspase- 8, -9, decrease cell viability. Colorectal (DLD- 1) [192]
31 Phenolics Protection of oxidative induced stress, reduced cell
damage.
32 Polysaccharides (PS) Involve defense mechanisms via phagocytosis Brain tumors [194]
33 Quercetin Inhibit p53 protein expression, arrest G2-M phase. Breast (MDA- MB468) [195]
34 Rhein Induced apoptosis, chemotaxis, and nitrate
production.
35 Tetrandrine,
fangchinoline
36 Triptolide Enhance p17 cleaved, and caspase 3 activity. Proximal tubular
Reduced P- gp expression MDR Caco- 2, and
Prostate (LNCaP) [187]
Breast (MCF- 7) [188]
Malignant (MCF- 7/
adr, MCF- 7).
Osteogenic (U- 2 OS,
HOS, and 143B).
Leukemia (CEM/
ADR5000)
Lung broblasts
(CCD- 25LU)
Colonic (CaCo- 2) [196]
ADR5000/CEM.
(HK- 2)
[186]
[189]
[190]
[191]
[193]
[197]
[198]
by Withania somnifera. Additionally, Actaea dahurica and Adina rubella extracts demonstrate anti-
tumor and anticancer activities, respectively [160].
Quercetin stops the growth of breast and liver cancer cells, and saponins have anticancer and
hypocholesterolemic properties. Triterpenes derived from Ganoderma lucidum exhibit substantial
pharmacological potential in cancer treatment since Ganodermanontriol inhibits the proliferation of
HCT116 and HT- 29 (colon cancer cells) [161]. While these triterpenes do not affect normal human
liver cells, they can cause apoptosis in many cancer cell lines, including hepatocellular carcinoma
(HuH- 7). Flavonoids and phenolics have anti- tumor and cytotoxic effects. Alkaloids that target cancer include paclitaxel, vinca alkaloids, and camptothecin [162]. In cancer therapy, alkaloids from
Chelidonium extracts inhibit ABC transporters in cancerous cells, whereas camptothecin inhibits
DNA topoisomerase. Many different plant compounds have to exhibit anticancer characteristics in
a variety of human cell lines [163].
5.9.3 bioacTive comPounds for neurodegeneraTive diseases
Natural plants are a crucial source of bioactive compounds historically used in medicine. They produce
SMs for defense and signaling, which often have signicant biological and pharmacological activities
[199]. These SMs are isolated for therapeutic uses, including oncology, due to their lower toxicity
and better patient acceptance. For example, paclitaxel and docetaxel, used in breast cancer treatment,
are derived from the Pacic yew tree (Taxus brevifolia) and the European yew tree (Taxus baccata),
106 Herbal Pharmacopeia
TABLE 5.7
Some Natural Bioactive Compounds for Neurodegenerative Diseases
S# Bioactive Compounds Source Effects Reference
01 Dihydromyricetin Ampelopsis
grossedentata
02 Flavonoids 1-9 Oxalis corniculate L. Inhibition of carbonic anhydrases II,
03 (-)-narcissidine,
(+)-9-O- demethyl- 2ahydroxyhomolycorine,
(-)-9-Omethylpseudolycorine,
(-)-pancratinine- C
04 Desmethoxyangonin Renealmia Alpinia Inhibition of monoamine oxidases
05 Emodin, Physcion,
Helminthosporin,
chryso- phanol
06 (-)-maackian and others S. avescens Inhibition of MAOs [211]
Narcissus tazetta L. Inhibition of BChE, and AChE [208]
Rumex abyssinicus Inhibition of BChE and AChE [210]
Inhibition and neuroprotective activity of
α-synuclein bril formation
butyrylcholine esterase (BChE), and
acetylcholine esterase (AChE)
(MAOs)
[206]
[207]
[209]
respectively. Additionally, the vinblastine and vinca alkaloids vincristine from the periwinkle plant
Catharanthus roseus, are used in anticancer treatments [200, 201].
Polyphenols are a class of plant- derived secondary metabolites (SM) with protective effects against
neurodegenerative disorders, diabetes, cardiovascular diseases, and cancer. They include coumarins,
avonoids, lignins, stilbenes, phenolic acids and tannins [202]. Coumarins are found in plants like
Melilotus sp., Galium odoratum, Dichanthelium clandestinum, Hierochloe odorata, Anthoxanthum
odoratum, Dipteryx odorata, and Verbascum spp. [203]. Resveratrol, a stilbenoid in fruits and plants
like Vitis vinifera and Polygonum cuspidatum, has various biological properties, including neuropro-
tective effects [201].
The treatment and prevention of neurodegenerative diseases like Alzheimer’s and Parkinson’s are
crucial due to their rising prevalence in the aging population [204]. Their multifactorial nature complicates diagnosis and treatment, with few available drugs. Lifestyle factors, including diet, inuence their development, highlighting the role of plant SMs in maintaining nervous system health
[205]. Table 5.7 summarizes research on plant SMs with potential activity against neurodegenerative diseases. Various foods and drinks have shown signicant antioxidant properties, and recent
studies have explored different and novel sources [201].
5.9.4 bioacTive comPounds for viral diseases
Human immunodeciency virus (HIV) causes acquired immune deciency syndrome (AIDS), with
heterosexual sex being the predominant global transmission route, accounting for approximately
87% of cases, as noted by the National AIDS Control Organization (NACO) [212]. HIV can be
transmitted from mother to child and through blood products. Once inside the body, it uses CD4
receptors and either CXCR4 or CCR5 to multiply in macrophages or CD4+ cells. HIV- 1 gradually
increases in lymphoid tissues, which causes an increasing decline in immunity and ultimately results
in AIDS [213]. The risk of opportunistic infections and neoplasia rises with a decline in CD4+
helper cell counts below 200 cells/mm3 and an increase in plasma HIV- RNA levels [212]. These
processes are caused by activation- induced cell death (AICD) and apoptosis, which also impact
Bioactive Compounds in Herbal Remedies 107
non- infected cells. Highly active antiretroviral therapy (HAART) employing protease inhibitors and
reverse transcriptase analogs, either nucleoside or non- nucleoside, has been the latest treatment for
HIV. HAART successfully inhibits HIV- 1 replication; however, additional inhibitors are required
for drug- resistant patients. Although these medications aid in immune response modulation, their
toxicity limits their long- term efcacy [214].
In HIV/AIDS patients, several medicinal plants prevent the spread of the virus and strengthen the
immune system against opportunistic infections. Given the genetically diverse RNA genome of HIV,
herbal plants’ active compounds present an economical and efcient substitute that may possess
anti- retroviral characteristics. Herbal therapy, though historically limited, is regarded as a complementary medicine for HIV and several viral infection patients in Europe [215]. Herbalists use these
plants to provide alternative or supplemental treatments in addition to HIV/AIDS medications
(Table 5.8). Active compounds from plants, such as glycyrrhizin from Glycyrrhiza uralensis and
Moringa oleifera, have shown efcacy in enhancing immune function in HIV patients [216]. Plantbased bioactive compounds like avones, tannins, polysaccharides, alkaloids, coumarins, lignans,
and terpenes exhibit antiviral properties, making them promising candidates for developing new
herpes simplex virus (HSV), Epstein–Barr Virus [217], anti- HIV, hepatitis C virus (HCV), and
respiratory syncytial virus (RSV) therapies [213].
Hepatitis is a severe and potentially fatal disease that causes liver inammation, posing signicant health risks. It is commonly known as viral hepatitis and can cause an estimated mortality of
1–4 million annually worldwide [218]. Various viruses, like Herpes simplex, Epstein- Barr, and
Cytomegalovirus, can cause liver inammation, but hepatitis viruses A, B, C, D, and E are the primary culprits. Types B, C, and E can cause chronic hepatitis, which can progress to potentially fatal
disorders, including liver cirrhosis or hepatocellular carcinoma [219]. Natural materials derived
from plants, herbs, and animals have been utilized recently to create novel antiviral medications to
treat viral hepatitis [220]. Medicinal plants provide an economical and low- side- effect treatment
option, and, due to the higher toxicity of chemical drugs, the use of more efcient herbal products
has increased over the last decade. These natural compounds show signicant antiviral effects by
interfering with various stages of lifecycle of the hepatitis virus, including replication, viral release,
and host- specic interactions [218].
TABLE 5.8
The Effectiveness of Some Medicinal Herbal Plants in HIV and Hepatitis Inhibition
and Control in Humans
S# Plant Name Mechanism/Bioactivity References
01 Ancistrocladus kor Inhibits reverse transcriptase [221]
02 Banksia micrantha RNAse H Pascal activity and RDDP inhibition of HIV- 1 RT [222]
03 Curcuma longa Inhibition of HIV integrase [223]
04 Dryopteris crassirhizoma Ant- HIV- 1 protease activity [224]
05 Epimedium grandiorum Inhibitory activity against HIV [225]
06 Flammulina velutipes HIV- 1 RT Inhibition [226]
07 Myrothamnus abellifolius
Blueberry
08
09 W. chamaedaphne Exhibited strong anti- HBV activity [218]
10 M. peregrinum
Proanthocyanidins
Anti- HIV RT action of free radicals is blocked by polyphenols on
cell membranes
Interruption of binding of HAV and its entry into the cell [228]
Inhibited HCV infection and efcient against all major HCV
genotypes
[227]
[229]
108 Herbal Pharmacopeia
5.9.5 anTi- inflammaTory bioacTive comPounds in herbs
Inammation is a multifaceted biological defense mechanism that involves molecular mediators,
blood vessels, and immune cells in the body’s tissues in reaction to tissue damage, microbial infection, or irritants [230]. Natural products have recently been discovered to have anti- inammatory
properties, providing comprehensive explanations in addition to molecular docking techniques for
substances that occur naturally. Research has documented the anti- inammatory properties of certain
herbs, including Zingiber ofcinale, Borago ofcinalis, Rosmarinus ofcinalis, and Curcuma longa
[47]. These plants hold potential therapeutic use in various clinical contexts. Recently, the development of anti- inammatory compounds derived from plant SMs has shown notable effectiveness
[231]. These compounds include fatty acids, terpenes, polyphenols, and many other bioactive components. Specically, Aswad et al. reported that numerous plant SMs that are derived from chili peppers, Erythrina velutina, and Zanthoxylum beecheyanum [47], respectively, such as moupinamide,
capsaicin, and hypaphorine, can be employed as novel, potential anti- inammatory medicines [232].
5.9.6 anTidiabeTic bioacTive comPounds in herbs
Diabetes mellitus (DM) is a metabolic disease dened by persistently high levels of blood sugar and
abnormalities in the metabolism of fats, proteins, and carbohydrates as a result of deciencies in the
secretion or action of insulin. Multiple organ failure, malfunction, and long- term damage are caused
by diabetic mellitus. There are three main types of DM [233]: Insulin- dependent type 1 diabetes is
an autoimmune disease in which the pancreas's insulin- producing cells are destroyed, resulting in
little or no insulin production. DM (type 1) typically affects children and young adults and requires
daily insulin doses. Type 2 diabetes (insulin- independent): Accounts for over 90% of adult DM
cases [234]. The body’s inability to effectively use the ample insulin produced by the pancreas is
known as insulin resistance. Gestational DM is a common metabolic condition during pregnancy
that is characterized by glucose intolerance that is initially identied during the second or third
trimester of pregnancy and is caused by either a shortage of insulin or pregnancy hormones [232].
Hyperglycemia causes damage to blood vessels, kidneys, eyes, heart, and nerves. Recently, many
medicinal plants have shown antidiabetic and antihyperlipidemic properties. There are around 400
known plant species that have hypoglycemia activity, and because natural plants include safe and
useful phytoconstituents such as phenolics, alkaloids, terpenoids, avonoids, and carotenoids, there
is continued interest in developing new antidiabetic medications from these sources; a few of these
are listed in Table 5.9 [232]. Because of their greater body compatibility, lower side effects, and
cultural acceptability, these medications are frequently used for primary healthcare [235].
5.9.7 anTibioTics
Antibiotic actions are demonstrated by numerous plant SMs against diverse pathogenic microorganisms, targeting key cellular processes including protein assimilation, DNA/RNA replication, and
TABLE 5.9
The Antidiabetic Effects of Common Bioactive Compounds
S# Compounds Antidiabetic Properties
01 Momordin
02 Polypeptide- p Decrease blood glucose level, function as a protein similar to insulin.
03 Saponins Reduce blood sugar and increase insulin production
04 Conjugated linolenic acid (9c, 11t, 13t)
05 Momordicosides Enhance the uptake of glucose
PPAR δ activation
Activation of PPAR δ
Bioactive Compounds in Herbal Remedies 109
cell wall synthesis. For centuries, the food industry, agriculture, and pharmacology have used plantderived natural products to control phytopathogens, weeds, and insects, and to preserve food and
develop medicines [236]. Many bioactive compounds from medicinal plants, such as alkaloids like
sanguinarine from the Papaveraceae family and berberine from Berberis spp., and avonoids like
quercetin and kaempferol from Camellia sinensis and Allium cepa, respectively, have signicant
antibacterial activity by inhibiting enzymes and disrupting cell membranes. From natural sources,
notable recent antibiotics include retapamulin (2007), daptomycin (2003), and daxomicin (2010)
[47]. Twelve antibiotics received medical approval between 1935 and 1968; however, between 2003
and 2015, the number of approvals rose to 20, with 16 of those being derived from natural sources.
In 2018, Cragg and Newman reported changes to aminoglycosides that produced eravacycline, omadacycline, lefamulin, and sarecycline. They also highlighted plant SMs having antibacterial action,
such as sisomicin and plazomicin [237]. Medicinal plant bioactive compounds possess antifungal
properties. Green tea’s polyphenols, such as epigallocatechin gallate (EGCG), inhibit the growth of
many fungal species (e.g., Aspergillus and Candida), while the EOs of tea tree and oregano demonstrate potent antifungal effects against a range of pathogenic fungi [47, 238].
5.10 SUMMARY
This chapter explores the potential of herbal drugs and bioactive compounds in human healthcare,
gathering information on herbal compounds and related products that demonstrate their ability to
halt or slow the progression of fatal diseases. Natural products are nature- derived compounds that
generally possess pharmacological or biological properties, making them essential in pharmaceutical drug design and discovery. Phytochemicals are classied into primary metabolites, such as amino
acids, carbohydrates, chlorophylls, and proteins, and Secondary metabolites, such as terpenoids,
tannins, alkaloids, saponins, avonoids, steroids and their glycosides, etc. In animal models, herbal
compounds have demonstrated therapeutic results in the treatment of sarcomas, leukemia, and skin
cancer. These compounds are used in conjunction with chemotherapy to minimize adverse effects
in cancer patients. Research has shown that herbs can help control antimicrobial and viral disease,
nonetheless, there is still insufcient knowledge regarding the clinical efcacy and toxicity of many
herbal medications, and, despite being the world’s leading cause of death, little is known about their
potential anticancer properties. Therefore, identifying new compounds in herbs and understanding
their mechanisms are crucial for evaluating their potential clinical applications.
LIST OF ABBREVIATIONS
ACE2 Angiotensin- Converting Enzyme 2
AICD Activation- Induced Cell Death
AIDS Acquired Immune Deciency Syndrome
CD4 Cluster of Differentiation 4
CNS Central Nervous System
DM Diabetes Mellitus
EGCG Epigallocatechin gallate
EOs Essential Oils
FDA Food and Drug Administration
FTIR Fourier- Transform Infrared Spectroscopy
HAART Highly Active Antiretroviral Therapy
HCV Hepatitis C Virus
HIV Human Immunodeciency Virus
HPLC High- Performance Liquid Chromatography
HSV Herpes Simplex Virus
IFN- γ Interferon- γ
110 Herbal Pharmacopeia
IgG Immunoglobulin G
IgM Immunoglobulin M
MEP Methylerythritol 4-Phosphate
MHC Major Histocompatibility Complex
NACO National AIDS Control Organization
NF- κ Nuclear Factor kappa
NK Natural Killer Cell
NO Nitric Oxide
PBMCs Peripheral Blood Mononuclear Cells
PCs Phenolic Compounds
RNA Ribonucleic Acid
ROS Reactive Oxygen Species
RSV Respiratory Syncytial Virus
SMs Secondary Metabolites
TCM Traditional Chinese medicine
TH2 T Helper cell type 2
TLC Thin Layer Chromatography
TNF- α Tumor Necrosis Factor alpha
USA United States of America
WHO World Health Organization
REFERENCES
1. Biselli, R.; Nisini, R.; Lista, F.; Autore, A.; Lastilla, M.; De Lorenzo, G.; Peragallo, M. S.; Stroffolini,
T.; D’Amelio, R. A historical review of military medical strategies for ghting infectious diseases: From
battleelds to global health. Biomedicines. 2022, 10(8), 2050.
2. Muteeb, G.; Rehman, M. T.; Shahwan, M.; Aatif, M. Origin of antibiotics and antibiotic resistance, and
their impacts on drug development: A narrative review. Pharmaceuticals. 2023, 16(11), 1615.
3. Lewis, K. The science of antibiotic discovery. Cell. 2020, 181(1), 29–45.
4. Chawla, M.; Verma, J.; Gupta, R.; Das, B. Antibiotic potentiators against multidrug- resistant bacteria:
discovery, development, and clinical relevance. Frontiers in Microbiology. 2022, 13, 887251.
5. Mog, M.; Ngasotter, S.; Tesia, S.; Waikhom, D.; Panda, P.; Sharma, S.; Varshney, S. Problems of antibi-
otic resistance associated with oxytetracycline use in aquaculture: A review. Journal of Entomology and
Zoology Studies. 2020, 8, 1075–1082.
6. Jamal, A. Embracing nature's therapeutic potential: Herbal medicine. International Journal of
Multidisciplinary Sciences and Arts. 2023, 2(1), 117–126.
7. Balunas, M. J.; Kinghorn, A. D. Drug discovery from medicinal plants. Life Sciences. 2005, 78(5),
431–441.
8. Dutra, R. C.; Campos, M. M.; Santos, A. R.; Calixto, J. B. Medicinal plants in Brazil: Pharmacological
studies, drug discovery, challenges and perspectives. Pharmacological Research. 2016, 112, 4–29.
9. Wu, M.; Su, X.; Wu, Y.; Luo, Y.; Guo, Y.; Xue, Y. Glycosylated coumarins, avonoids, lignans and
phenylpropanoids from Wikstroemia nutans and their biological activities. Beilstein Journal of Organic
Chemistry. 2022, 18(1), 200–207.
10. Hao, X.; Sun, W.; Ke, C.; Wang, F.; Xue, Y.; Luo, Z.; Wang, X.; Zhang, J.; Zhang, Y. Anti-Inammatory
Activities of Leaf Oil from Cinnamomum subavenium In Vitro and In Vivo. BioMed Research
International. 2019, 2019(1), 1823149.
11. Praveen, N.; Preetha, R. S. T.; Pagare, V.; Devasia, J.; Nizam, A.; Mukherjee, E.; Vasantha, V. L.;
Al- Khayri, J. M. Plant- based Metabolites as Source of Antimicrobial Therapeutics: Prospects and
Challenges. Antimicrobials in Pharmaceutical and Medicinal Research. 2023, 165–201.
12. Mehrotra, N. Herbs that heal: Nature’s pharmacy endowed remedies for better health. Annals of
Phytomedicine. 2021, 10(1), 6–22.
13. Khare, T.; Anand, U.; Dey, A.; Assaraf, Y. G.; Chen, Z.-S.; Liu, Z.; Kumar, V. Exploring phytochemi-
cals for combating antibiotic resistance in microbial pathogens. Frontiers in Pharmacology. 2021, 12,
720726.
Bioactive Compounds in Herbal Remedies 111
14. Alara, J. A.; Alara, O. R. An Overview of the Global Alarming Increase of Multiple Drug Resistant:
AMajor Challenge in Clinical Diagnosis. Infectious Disorders- Drug Targets. 2024, 24(3), 26–42.
15. Wu, L.; Chen, W.; Wang, Z. Traditional Indian medicine in China: The status quo of recognition, devel-
opment and research. Journal of Ethnopharmacology. 2021, 279, 114317.
16. Goyal, S.; Thirumal, D.; Yapar, E. A.; Gürer, E. S.; Kumar, A.; Babu, M. A.; Sindhu, R. K. Asian Veterinary
Medicines: From the Past to the Future. Journal of Research in Pharmacy. 2023, 27(4), 1313–1328.
17. Mostafa, S.; Wang, Y.; Zeng, W.; Jin, B. Floral scents and fruit aromas: Functions, compositions, biosyn-
thesis, and regulation. Frontiers in Plant Science. 2022, 13, 860157.
18. Sarkar, M.; Talukder, P. Role of Plant Metabolites in Curing Neurodegenerative Disorders. American
Journal of Applied Bio- Technology Research. 2023, 3(4), 34–45.
19. Wu, Y.; Su, X.; Lu, J.; Wu, M.; Yang, S. Y.; Mai, Y.; Deng, W.; Xue, Y. In Vitro and in silico analysis of
phytochemicals from fallopia dentatoalata as dual functional cholinesterase inhibitors for the treatment
of Alzheimer’s disease. Frontiers in Pharmacology. 2022, 13, 905708.
20. Chaachouay, N.; Zidane, L. Plant- derived natural products: a source for drug discovery and development.
Drugs and Drug Candidates. 2024, 3(1), 184–207.
21. Ashraf, M. V.; Pant, S.; Khan, M. H.; Shah, A. A.; Siddiqui, S.; Jeridi, M.; Alhamdi, H. W. S.; Ahmad, S.
Phytochemicals as antimicrobials: prospecting Himalayan medicinal plants as source of alternate medicine to combat antimicrobial resistance. Pharmaceuticals. 2023, 16(6), 881.
22. Napagoda, M.; Wijesundara, D. Medicinal plants as sources of novel therapeutics: The history, present,
and future. Chemistry of Natural Products, Phytochemistry and Pharmacognosy of Medicinal Plants.
2022, 3, 4–18.
23. Usha, P.; Jose, S.; Nisha, A. Antimicrobial Drug Resistance – A global concern. Veterinary World. 2010,
3(3), 138–139.
24. Kotwal, S.; Borude, P.; Humbe, T. A review: Most permitted traditional systems of Indian culture. World
Journal of Pharmaceutical Research. 2021, 10(5), 1112–1124.
25. McMullen, R. L.; Dell’Acqua, G. History of natural ingredients in cosmetics. Cosmetics. 2023, 10(3), 71.
26. Parveen, B.; Parveen, A.; Parveen, R.; Ahmad, S.; Ahmad, M.; Iqbal, M. Challenges and opportunities for
traditional herbal medicine today, with special reference to its status in India. Ann Phytomed. 2020, 9(2),
97–112.
27. Sinha, D.; Odoh, U. E.; Ganguly, S.; Muhammad, M.; Chatterjee, M.; Chikeokwu, I.; Egbuna, C.,
Phytochemistry, history, and progress in drug discovery, in Phytochemistry, Computational Tools and
Databases in Drug Discovery. 2023, Elsevier. pp. 1–26.
28. Jitareanu, A.; Trifan, A.; Vieriu, M.; Caba, I.-C.; Mârtu, I.; Agoroaei, L. Current trends in toxicity assess-
ment of herbal medicines: A narrative review. Processes. 2022, 11(1), 83.
29. Liang, Z.; Hu, H.; Li, J.; Yao, D.; Wang, Y.; Ung, C. O. L. Advancing the regulation of traditional and
complementary medicine products: A comparison of ve regulatory systems on traditional medicines
with a long history of use. Evidence-Based Complementary and Alternative Medicine. 2021, 2021(1),
5833945.
30. Malik, A.; Pereira, V.; Budhwar, P.; Varma, A.; Del Giudice, M. Sustainable innovations in an indigenous
Indian Ayurvedic MNE. Journal of Business Research. 2022, 145, 402–413.
31. Qadir, S. U.; Raja, V., Herbal medicine: Old practice and modern perspectives, in Phytomedicine. 2021,
Elsevier. pp. 149–180.
32. Najmi, A.; Javed, S. A.; Al Bratty, M.; Alhazmi, H. A. Modern approaches in the discovery and devel-
opment of plant- based natural products and their analogues as potential therapeutic agents. Molecules.
2022, 27(2), 349.
33. Nasim, N.; Sandeep, I. S.; Mohanty, S. Plant- derived natural products for drug discovery: current
approaches and prospects. The Nucleus. 2022, 65(3), 399–411.
34. Dzobo, K. The role of natural products as sources of therapeutic agents for innovative drug discovery.
Comprehensive Pharmacology. 2022, 408. 10.1016/B978-0-12-820472-6.00041-4
35. Berdigaliyev, N.; Aljofan, M. An overview of drug discovery and development. Future Medicinal
Chemistry. 2020, 12(10), 939–947.
36. Motyka, S.; Jafernik, K.; Ekiert, H.; Shari- Rad, J.; Calina, D.; Al- Omari, B.; Szopa, A.; Cho, W. C.
Podophyllotoxin and its derivatives: Potential anticancer agents of natural origin in cancer chemotherapy.
Biomedicine and Pharmacotherapy. 2023, 158, 114145.
112 Herbal Pharmacopeia
37. Bairagi, B.; Ali, M. Z.; Tiwari, H. Rauwola serpentina: A review on biological and medicinal properties.
European Journal of Modern Medicine and Practice. 2024, 4(6), 523–529.
38. Deep, A.; Kumar, D.; Bansal, N.; Narasimhan, B.; Marwaha, R. K.; Sharma, P. C. Understanding mecha-
nistic aspects and therapeutic potential of natural substances as anticancer agents. Phytomedicine Plus.
2023, 3(2), 100418.
39. Mustafa, G.; Arif, R.; Atta, A.; Sharif, S.; Jamil, A. Bioactive compounds from medicinal plants and their
importance in drug discovery in Pakistan. Matrix Science Pharma. 2017, 1(1), 17–26.
40. Twaij, B. M.; Hasan, M. N. Bioactive secondary metabolites from plant sources: types, synthesis, and
their therapeutic uses. International Journal of Plant Biology. 2022, 13(1), 4–14.
41. Noman, A.; Aqeel, M.; Qasim, M.; Haider, I.; Lou, Y. Plant- insect- microbe interaction: A love triangle
between enemies in ecosystem. Science of the Total Environment. 2020, 699, 134181.
42. Lv, M.; Sun, D.-W.; Huang, L.; Pu, H. Precision release systems of food bioactive compounds based
on metal- organic frameworks: synthesis, mechanisms and recent applications. Critical Reviews in Food
Science and Nutrition. 2022, 62(15), 3991–4009.
43. Khare, S.; Singh, N.; Singh, A.; Hussain, I.; Niharika, K.; Yadav, V.; Bano, C.; Yadav, R. K.; Amist, N.
Plant secondary metabolites synthesis and their regulations under biotic and abiotic constraints. Journal
of Plant Biology. 2020, 63, 203–216.
44. Rautela, A.; Kumar, S. Engineering plant family TPS into cyanobacterial host for terpenoids production.
Plant Cell Reports. 2022, 41(9), 1791–1803.
45. Li, H.; Yang, Q.; Fan, N.; Zhang, M.; Zhai, H.; Ni, Z.; Zhang, Y. Quantitative trait locus analysis of het-
erosis for plant height and ear height in an elite maize hybrid zhengdan 958 by design III. BMC Genet.
2017, 18, 1–10.
46. Wang, L.; Wu, L. M.; Greaves, I. K.; Dennis, E. S.; Peacock, W. J. In Arabidopsis hybrids and Hybrid
Mimics, up-regulation of cell wall biogenesis is associated with the increased plant size. Plant Direct.
2019, 3(11), e00174.
47. Elshae, H. S.; Camele, I.; Mohamed, A. A. A comprehensive review on the biological, agricultural
and pharmaceutical properties of secondary metabolites based- plant origin. International Journal of
Molecular Sciences. 2023, 24(4), 3266.
48. Silva, A.; Silva, V.; Igrejas, G.; Aires, A.; Falco, V.; Valentão, P.; Poeta, P. Phenolic compounds classica-
tion and their distribution in winemaking by- products. European Food Research and Technology. 2023,
249(2), 207–239.
49. Prieto, J. M.; Schinella, G. R. Anti- inammatory and antioxidant Chinese herbal medicines: Links between
traditional characters and the skin lipoperoxidation “Western” model. Antioxidants. 2022, 11(4), 611.
50. Hassan, M. A.; Xu, T.; Tian, Y.; Zhong, Y.; Ali, F. A. Z.; Yang, X.; Lu, B. Health benets and phenolic
compounds of Moringa oleifera leaves: A comprehensive review. Phytomedicine. 2021, 93, 153771.
51. Shah, A.; Smith, D. L. Flavonoids in agriculture: Chemistry and roles in, biotic and abiotic stress
responses, and microbial associations. Agronomy. 2020, 10(8), 1209.
52. Dias, M. C.; Pinto, D. C.; Silva, A. M. Plant avonoids: Chemical characteristics and biological activity.
Molecules. 2021, 26(17), 5377.
53. Zhuang, W.-B.; Li, Y.-H.; Shu, X.-C.; Pu, Y.-T.; Wang, X.-J.; Wang, T.; Wang, Z. The classication,
molecular structure and biological biosynthesis of avonoids, and their roles in biotic and abiotic stresses.
Molecules. 2023, 28(8), 3599.
54. Roufogalis, B. Flavonoid pharmacokinetics: Methods of analysis, preclinical and clinical pharmacoki-
netics, safety, and toxicology. 2012. John Wiley & Sons.
55. Shakour, Z. T. A.; Fayek, N. M.; Farag, M. A. How do biocatalysis and biotransformation affect Citrus
dietary avonoids chemistry and bioactivity? Critical Reviews in Biotechnology. 2020, 40(5), 689–714.
56. Pal, D.; Sahu, P. Potential of Flavonoids in Viral Infection: From Ethnopharmacology to Clinical Trials
28. Anti- Viral Metabolites from Medicinal Plants. 2024, 1009. 10.1007/978-3-031-12199-9_28
57. Pal, D.; Sahu, P., Potential of Flavonoids in Viral Infection: From Ethnopharmacology to Clinical Trials,
in Anti- Viral Metabolites from Medicinal Plants. 2023, Springer. pp. 1009–1038.
58. Alamgir, A.; Alamgir, A. Vitamins, nutraceuticals, food additives, enzymes, anesthetic aids, and cosmet-
ics. Therapeutic Use of Medicinal Plants and their Extracts: Volume 2: Phytochemistry and Bioactive
Compounds. 2018, 407–534.
59. Roh, C. Microbial transformation of bioactive compounds and production of ortho- dihydroxyisoavones
and glycitein from natural fermented soybean paste. Biomolecules. 2014, 4(4), 1093–1101.
Bioactive Compounds in Herbal Remedies 113
60. Lalouckova, K.; Mala, L.; Marsik, P.; Skrivanova, E. In vitro antibacterial effect of the methanolic extract
of the Korean soybean fermented product doenjang against Staphylococcus aureus. Animals. 2021, 11(8),
2319.
61. Lerman, J. S.; Haslem, J.; Kim, L.; Ponderelli, J.; Ma, M.; Felson, R.; Sanderson, K.; Murphy, K.;
Hopkins, K.; Wright, E. Collected research on phytonutrients: Flavonoids. Journal of Culinary Science
and Technology. 2015, 13(3), 214–241.
62. Terahara, N. Flavonoids in foods: a review. Natural Product Communications. 2015, 10(3), 1934578
X1501000334.
63. Khoo, H. E.; Azlan, A.; Tang, S. T.; Lim, S. M. Anthocyanidins and anthocyanins: Colored pigments as
food, pharmaceutical ingredients, and the potential health benets. Food and Nutrition Research. 2017.
10.1080/16546628.2017.1361779
64. Dini, C.; Zaro, M. J.; Viña, S. Z. Bioactivity and functionality of anthocyanins: A review. Current
Bioactive Compounds. 2019, 15(5), 507–523.
65. Paulino, B. N.; Silva, G. N.; Araújo, F. F.; Néri- Numa, I. A.; Pastore, G. M.; Bicas, J. L.; Molina, G.
Beyond natural aromas: The bioactive and technological potential of monoterpenes. Trends in Food
Science and Technology. 2022, 128, 188–201.
66. Shin, S.-A.; Moon, S. Y.; Kim, W.-Y.; Paek, S.-M.; Park, H. H.; Lee, C. S. Structure- based classication
and anti- cancer effects of plant metabolites. International Journal of Molecular Sciences. 2018, 19(9),
2651.
67. Mabou, F. D.; Yossa, I. B. N. Terpenes: Structural classication and biological activities. IOSR Journal
of Pharmacy and Biological Sciences. 2021, 16, 25–40.
68. Ninkuu, V.; Zhang, L.; Yan, J.; Fu, Z.; Yang, T.; Zeng, H. Biochemistry of terpenes and recent advances
in plant protection. International Journal of Molecular Sciences. 2021, 22(11), 5710.
69. Runyoro, D.; Ngassapa, O.; Vagionas, K.; Aligiannis, N.; Graikou, K.; Chinou, I. Chemical composi-
tion and antimicrobial activity of the essential oils of four Ocimum species growing in Tanzania. Food
Chemistry. 2010, 119(1), 311–316.
70. Muhammed, D.; Odey, B. O.; Alozieuwa, B. U.; Alawode, R. A.; Okunlola, B.; Ibrahim, J.; Lawal, A.;
Berinyuy, E. B. Azadirachtin- A a bioactive compound from Azadirachta indica is a potential inhibitor of
SARS- CoV- 2 main protease. AROC in Pharmaceutical and Biotechnology. 2021, 1(1), 1–8.
71. Hassan, W.; Rehman, S.; Noreen, H.; Gul, S.; Neelofar, A. N. Gas chromatography mass spectrometric
(GCMS) analysis of essential oils of medicinal plants. Adv. Anim. Vet. Sci. 2016, 4(8), 420–437.
72. Karimkhani, M. M.; Nasrollahzadeh, M.; Maham, M.; Jamshidi, A.; Kharazmi, M. S.; Dehnad, D.; Jafari,
S. M. Extraction and purication of α-pinene; a comprehensive review. Critical Reviews in Food Science
and Nutrition. 2024, 64(13), 4286–4311.
73. Xu, J.; Wang, S.; Feng, T.; Chen, Y.; Yang, G. Hypoglycemic and hypolipidemic effects of total saponins
from Stauntonia chinensis in diabetic db/db mice. Journal of cellular and molecular medicine. 2018,
22(12), 6026–6038.
74. Ahmed, E.; Arshad, M.; Khan, M. Z.; Amjad, M. S.; Sadaf, H. M.; Riaz, I.; Sabir, S.; Ahmad, N.
Secondary metabolites and their multidimensional prospective in plant life. Journal of Pharmacognosy
and Phytochemistry. 2017, 6(2), 205–214.
75. Jan, B.; Choudhary, B.; Malik, Z.; Dar, M. I. A descriptive review on exploiting the therapeutic signi-
cance of essential oils as a potential nutraceutical and food preservative. Food Safety and Health. 2024,
2(2), 238–264.
76. Banday, A. H. Steroids and their Medicinal Potential. 2023. Bentham Science Publishers.
77. Nattagh-Eshtivani, E.; Barghchi, H.; Pahlavani, N.; Barati, M.; Amiri, Y.; Fadel, A.; Khosravi, M.; Talebi,
S.; Arzhang, P.; Ziaei, R. Biological and pharmacological effects and nutritional impact of phytosterols:
A comprehensive review. Phytother. Res. 2022, 36(1), 299–322.
78. Sharma, A.; Ramakrishnan, M.; Khanna, K.; Landi, M.; Prasad, R.; Bhardwaj, R.; Zheng, B.
Brassinosteroids and metalloids: regulation of plant biology. J. Hazard. Mater. 2022, 424, 127518.
79. Truchan, M.; Tkachenko, H.; Buyun, L.; Kurhaluk, N.; Góralczyk, A.; Tomin, V.; Osadowski, Z. J.
Antimicrobial Activities of Three Commercial Essential Oils Derived from Plants Belonging to
Family Pinaceae. Agrobiodiversity for Improving Nutrition, Health and Life Quality. 2019(3). https://
agrobiodiversity. uniag. sk/ scienticpapers/ article/ view/ 287