Review
Nat Prod Ind J, Volume: 13( 2)

Chemical Constituents of Terminalia chebula

*Correspondence:
Dr. Riaz M, Associate Professor, Department of Chemistry, University of Azad Jammu and Kashmir, Muzaffarabad, 13100, Pakistan, Tel: (92)334 9270235; E-mail: [email protected]

Received: June 06, 2017; Accepted: October 27, 2017; Published: October 31, 2017

Citation: Riaz M, Khan O, Sherkheli MA, et al. Chemical Constituents of Terminalia Chebula. Nat Prod Ind J. 2017;13(2):112

Abstract

Despite the revolutionary progress and discoveries, the challenge to combat newly emerged and discovered diseases remains unmet. Natural products are still the prime reservoirs for providing new and novel molecular skeletons as drug candidates and inspiration. Terminalia chebula showed promising anti-microbial and anti-viral potentials and about 133 natural products have already been isolated from T. chebula and importantly, its richness of variety of metabolic enzymes are biosynthesizing diverse variety of secondary metabolites with attractive novelty and variety, ranging from phenolic derivative to flavonoids and falvins, terpenoids to steroids, alkaloids, tannins and their derivatives and glycosides. Molecular topology and variety in functionalities of in its natural products are important, especially dealing with the variable and adaptive capabilities of viruses and microorganism generated diseases. Importantly, it is useful for natural product chemist to have the updated chemical constituents of T. chebula.

Keywords

Terminalia Chebula; Chemical constituents; Nature unique diverse and rich variety

Introduction

Despite of the investments and progress in molecular biology and drug discovery, several infections by pathogenic microbes are major threats for human life. Development of various anti-microbial drugs have meaningfully controlled several pathogenic diseases or made them less destructive. However, emerging resistance against existing antibiotics has made them less effective and is a major threat to the humanity. Therefore the new antibiotics are crucially required on War-footing for the discovery and development of new antibiotics. Prevention of infections, tracking the resistant strains and proper use of antibiotics would be important precautionary measures. Natural products played the fundamental role as traditional herbal medicine and remedies and through advancement in the knowledge and research gave birth to the specific molecular medicines which also enhanced the structural and mechanistic understandings of biochemical entities and processes [1,2]. A major number of drugs have been derived or inspired from natural products [3,4]. Pain relieving properties of the Willow’s bark lead to the discovery of acetylsalicylic acid (aspirin) [5]. The first antibiotic, penicillin, was isolated from a mold, penicillium and terpenoidal anti-cancer taxol was isolated from Taxus brefolia [6]. Structural and functional biology andmedicinal chemistry have rewarded with revolutionary drugs [7], however, pathogenic micro-organism are major global risk to human health [8]. A progressive microbial resistance is an alarming threat causing community-acquired infections and antibiotic failure. Plants have been and are still the major, rich and diverse source of variety of phytochemicals including potent anti-microbial molecules [9]. Interestingly and presumably, since plant extracts contain many phytochemicals therefore, using plant extracts may pose some difficulty against the development of bacterial resistance as compared to the single molecular drug. Plants have provided anti-AIDS agents as well as anti-cancer taxol and homoharringtonine, benzylisoquinoline, papaverine with high inhibition to the replication of many viruses (e.g. cytomegalovirus, measles and HIV), atropisomeric naphthylisoquinoline dimers, michellamines A, B and C showed potential HIV-1 and HIV-2 on human lymphoblastoid target cell in vitro. Low cost to benefit ratio of natural product derived drugs is another attraction [3].

Experimental

Terminalia chebula

Terminalia chebula is a large sized traditional medicinal plant that is found in Pakistan, India, China and Tibet. It belongs togenus Terminalia which contains 250 species widely distributed throughout the tropical areas of the world. Traditionally, it is being used to treat gastrointestinal and urinary tract diseases, fever, cough, diarrhea, wound infections, skin diseases, urinary tract infection and candidiasis [10]. T. chebula possesses effective anti-bacterial and anti-viral activity against various bacterial strains [11,12].

Rich, diverse and novel nature molecular engineering (chemical constituents) in Terminalia chebula

Terminalia chebula habitats in tropical and sub-tropical diverse climatic condition and also is rich with metabolic engineeringenzymes, therefore it is extremely rich and diverse precursor for variety of natural products belonging to the various classes with different levels of biosynthesis. Richness, diversity and novelty of tannins and their analogues in T. chebula is a complex challenge both in term of isolation and structural modification but is an opportunity for the organic and medicinal chemists to modulate various biological disorders, especially pathogenic diseases because of their structural properties. Opportunity by T. chebula, is not limited to the tannins but also is fascinating with the provision of its small bioactive molecules which are very attractive for medicinal chemists and R&D organizations. Additionally, the variety of different classes of bioactive natural products in T. chebula further attracts the focused researchers which include, flavonoids, flavins, terpenoids, steroids, various phenols, functionalized aliphatic molecules and their glycosides (Figures 1-8). Structural diversity and novelty of the nature’s molecular engineering in T. chebula, especially in terms of in their skeletons, functionalities and linkages, is fascinating and invite focused and applied research to exploit their benefits in the form of new drugs (especially, antibiotics) further studies [13-31]. In addition, we understand and strongly propose that the standardization, efficacy, safety studies and documentations of its herbal products as of urgent prime importance. Focused and guided phytochemical re-investigation would be important and rewarding (Tables 1 to 7).

natural-products-chemical-constituents

Figure 1: Structure of chemical constituents (Tannins) of Terminalia chebula (1-31).

natural-products-phenolic-carboxylic

Figure 2: Structure of Phenolic Carboxylic Compounds (32-37).

natural-products-Structure-Phenols

Figure 3: Structure of Phenols (39-40).

natural-products-Terpenoids-Triterpene

Figure 4: Structure of Terpenoids and Triterpene Saponins (41-59).

natural-products-Flavonoids

Figure 5: Structure of Flavonoids (60-66).

natural-products-Structures-Sterols

Figure 6: Structures of Sterols (67,68).

natural-products-miscellaneous-compounds

Figure 7: Structure of Miscellaneous compounds present in Terminalia chebula (69-75).

natural-products-chebula-fruit

Figure 7: Structures of Compounds isolated from Terminalia chebula fruit (76-132).

# Tannins References
1 Punicalagin ((2, 3-(S)-hexahydroxydiphenoyl-4, 6-(S, S)-gallagyl-D-glucose) [13]
2 terflavin A [13]
3 Terchebulin [13]
4 Terchebin (1, 3, 6-trigalloyl glucose,) [14]
5 Terflavins B [13]
6 Terflavin C [13]
7 Terflavin D [13]
8 Punicalin [13]
9 Neo-chebulic acid [15]
10 X+ [15]
11 1, 6-di-O-galloyl-D-glucose [16]
12 Gallic acid (3, 4, 5-Trihydroxybenzoic acid) [16]
13 Casuarinin [16]
14 Chebulanin [16]
15 Corilagin [16]
16 Ellagic acid (2, 3, 7, 8-Tetrahydroxy-chromeno [5, 4, 3-cde]chromene-5, 10-dione) [16]
17 Chebulagic acid [16]
18 Chebulinic acid (1, 3, 6-Tri-O-galloyl-2, 4-chebuloyl-β-D-glucopyranoside) [16]
19 1, 2, 3, 4, 6-penta-O-galloyl-D-glucose [16]
20 2, 3, 4, 6-tetra-O-galloyl-B-D-glucose [17]
21 Ethyl gallate (Ethyl 3, 4, 5-trihydroxybenzoate) [17]
22 Methyl gallate (Methyl-3, 4, 5-trihydroxybenzoate) [17]
23 Chebulaginic acid [14]
24 4-O-methylgallic acid [18]
25 Methyl(S)-flavogallonate [18]
26 Methyl neochebulagate [18]
27 Eugenol [19]
28 Ascorbic acid [19]
29 Triethyl chebulate [20]
30 Tannic acid [2, 3-dihydroxy-5-({[(2R,3R,4S,5R,6R)-3, 4, 5, 6-tetrakis({3, 4-dihydroxy-5-[(3, 4, 5-trihydroxyphenyl)carbonyloxy]phenyl}carbonyloxy)oxan-2-yl]methoxy}carbonyl)phenyl 3, 4, 5-trihydroxybenzoate] [20]
31 2, 4-Chebulyl-beta-D-glucopyranose [13]

Table 1: Chemical constituents of Terminalia chebula.

# Phenolic Carboxylic compounds References
32 Shikimic acid [20]
33 Ferulic acid [20]
34 Vanillic acid [20]
35 p-Coumaric acid [20]
36 Caffeic acids [20]
37 Melilotic acid [21]

Table 2: Phenolic Carboxylic compounds from Terminalia chebula.

No. Phenols References
38 Phloroglucinol [benzene-1, 3, 5-triol ] [21]
39 Pyragallol [1, 2, 3-Trihydroxybenzene] [21]
40 Phenol [22]

Table 3: Phenols from Terminalia chebula.

# Terpenoids and Triterpene Saponins Ref.
41 Arjungenin [18]
42 Arjunolic acid [18]
43 Arjunic acid [18]
44 Terminolic acid [18]
45 Arjunglucoside I [18]
46 Arjunglucoside II [18]
47 Arjunetin [18]
48 Chebuloside II [18]
49 Bellericoside [23]
50 Chebuloside I [2α, 3β, 23-Trihydroxy-olean-12-en-28-oic Acid] [24]
51 2α-Hydroxyursolic acid [24]
52 2α-Hydroxymicromiric acid [24]
53 Maslinic acid [(4aS, 6aR, 6aS, 6bR, 8aR, 10R, 11R, 12aR, 14bS)-10, 11-dihydroxy-2, 2, 6a, 6b, 9, 9, 12a-heptamethyl-1, 3, 4, 5, 6, 6a, 7, 8, 8a, 10, 11, 12, 13, 14b-tetradecahydropicene-4a-carboxylic acid] [24]
54 β-caryophyllene [25]
55 α-Phellandrene[α: 2-Methyl-5-(1-methylethyl)-1, 3-cyclohexadiene] [25]
56 α-Terpinene [25]
57 Terpinen-4-ol [25]
58 Terpinolene [25]
59 Chebupentol [Olean-12-ene-2, 3, 19, 23, 28-pentol,(2a, 3b, 4a, 19a)] [25]

Table 4: Triterpenoids and their Saponins from Terminalia chebula.

# Flavonoids References
60 Rutin [25]
61  Quercetin [25]
62 Luteolin [2-(3, 4-Dihydroxyphenyl)-5, 7-dihydroxy-4-chromenone] [26]
63 Isoquercetin [2-(3, 4-Dihydroxyphenyl)-5, 7-dihydroxy-3-[(2S, 3R, 4S, 5S, 6R)-3, 4, 5-Trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxychromen-4-one] [26]
64 3’-Methoxy quercetin [13]
65 3, 4-Dimethoxy quercetin [5, 7-Dihydroxy-2-(3-hydroxy-4-methoxyphenyl)-3-Methoxy-4H-chromen-4-one] [13]
66 Pelargonidin [13]

Table 5: Flavonoids isolated from Terminalia chebula.

# Sterols References
67 β-Sitosterol [19]
68 Daucosterol [27]

Table 6: Sterols isolated from Terminalia chebula.

No.  Miscellaneous compounds References
69 Behenic acid [Docosanoic acid] [25]
70 Stearic acid [Octadecanoic acid] [25]
71 Palmitic acid [hexadecanoic acid] [14,22]
72 Oleic acid [(9Z)-Octadec-9-enoic acid] [14,22]
73 Arachidic acid [icosanoic acid] [14,22]
74 Linoleic acid [9Z, 12Z)-9, 12-Octadecadienoic acid] [14,22]
75 12-Hydroxyoctadec-cis-9-enoic acid (ricinoleic acid) [21]

Table 7: Miscellaneous compounds from Terminalia chebula.

No. Compound isolate from Terminalia chebula fruit Ref.
76 2-Undecanone [22]
77 Cyclododecane [22]
78 9-Octadecene [22]
79 Hexadecane [22]
80 Cylohexane [22]
81 8-Pentadecanone [22]
82 9-Eicosene [22]
83 Triacontane [22]
84 Tetradecane [22]
85 Oxirane [22]
86 1, 16-Hexadecanediol [22]
87 Heptylcyclohexane [22]
88 10-Nonadecanone [22]
89 Phthalic acid [22]
90 Tritetracontane [22]
91 9-Heptadecanone [22]
92 Tetratetracontane [22]
93 Linoleic acid ethyl ester [22]
94 9-Octadecenoic acid ethyl ester [22]
95 9, 12, 15-Octadecatrienoic acid [22]
96 1-Tricosene [22]
97 1, 19-Eicosadiene [22]
98 Heptafluorobutyric acid [22]
99 1-Octanol [22]
100 1-Decanol [22]
101 Cyclooctacosane [22]
102 1H-Indene [22]
103 Hexacosyl pentafluoropropionate [22]
104 Octatriacontyl pentafluoroprppionate [22]
105 Tetratriacontane [22]
106 1, 2-benzenedicarboxylic acid [22]
107 Ibogamin-9(17H)-ol [(9α)-12-Methoxy-16, 17-didehydro-9, 17-dihydroibogamin-9-ol] [22]
108 9-Tricosene [22]
109 Tetratriacontyl heptafluorobutyrate [22]
110 Dotricontyl heptafluorobutyrate [22]
111 Tetracosanoic acid [Lignoceric acid] [22]
112 Pentatriacontane [22]
113 Eicosyl trifluoroacetate [22]
114 Squalene [22]
115 Tetracosyl heptafluorobutyrate [22]
116 Tetratriacontyl heptafluorobutyrate [22]
118 Heptafluorobutyric acid [22]
119 Sulfurous acid [22]
120 Octacosanoic acid [22]
121 Vitamin E [22]
122 Tetracosyl heptafluorobutyrate [22]
123 Hexacosanoic acid [22]
124 Octatriacontyl pentafluoropropionate [22]
125 Triacontanoic acid [Melissic acid] [22,25]
126 Tricosyl pentafluoropropionate [22]
127 Acetic acid [22]
128 Heptacosanoic acid [22]
129 Tetratriacontyl pentafluoropropionate [22]
130 Tetracosanoate [22,28,29]
131 Kaempferol-3-rutinoside [22,30]
132 Ethanedioic acid [22,31]

Table 8: Compounds from Terminalia chebula fruit.

Results, Discussion and Conclusion

In light of role of nature engineered secondary metabolites in pharmaceuticals, the structural and functional diversity and novelty of natural products of Terminalia chebula along with the rich and diverse biosynthesis, together with their wide range of therapeutic applications and importantly its valuable anti-pathogenic biological properties coupled with the burnings needs for new antibiotics, we conclude and propose:

1. Focused and guided phytochemical re-investigations on the Terminalia chebula and its herbal products,

2. Structure activity relation (SAR) further medicinal chemistry to explore the drug potentials of already known bioactive molecules of Terminalia chebula, especially anti-microbial agents.

Further studies for the standardization, formulation, documentation, efficacy and safety of traditional herbal medicinal products (THMPs) of Terminalia chebula . Hence, it is crucial to be shared with the relevant scientists.

References